The transcript of the lecture posted yesterday

[Guest guest]

Guys

I understand that the lecture posted yesterday was to CSF people and about how

XMRV would effect this group but if this new bug is a key factor in Autism this

same information may well be pertinent to all of us!

The CFS chat group transcribed the lecture using different members for different

sections but I cut and pasted the various parts together. There are typos and

inaccuracies but all in all it is very enlightening!

Klimas

Section 1

Dr. Klimas

“Thank You.

So what brings us here today is this new discovery that you all might have seen

in the paper.

(skips)

Erm, let's. Can you just dim the lights down so that people can see that slide

OK. That's great, super.

So let's just go ahead and get stared.

I'm starting with a little background stuff.

There's three parts to my talk, OK.

Part 1, a little background for those of you who that are sort of new to the

world and don't realise all the work that's been going on.

Part 2, all about this virus and it's implications. Most of my talk's about

that.

Part 3, is plenty of time for questions and answers, so there's going to be a

lot of informal time. That's usually the best anyway, so if I get too long

winded, you all can just tell me to stop.

(laughs)

I do get excited.

(Image of four faces shown, with text above:

“CFS/ME and Viruses

Chronic Fatigue Syndromeâ€)

Some of you might recognise this. This is the CFS faces project from the CFIDS

Association, the CAA. It's a really neat thing they have that goes around the

country and shows up in shopping malls. But the point of the faces project is

that it's an invisible illness. The people that have this illness look fine, but

they are not fine. And it's a very important message, because Chronic Fatigue

Syndrome's a very debilitating condition.

And there's been research that looked at how severely ill people are with

Chronic Fatigue Syndrome.

And it was the same, or worse than, congestive heart failure.

The same, or worse than, very late stage AIDS.

It's very impressive how very ill people are.

And of course, most of you all are living it, but some of you might not realise

that the science bears that out.

It's been a hard illness to understand, because we had to diagnose it by

symptoms only, OK.

But the symptoms are pretty impressive, and some things are special, to really

help make the diagnosis.

One is the profound nature of the fatigue. It's not that 'Oh I'm tired to

fatigue', it's the profoundly debilitating fatigue that prevents you from being

able to do the normal things that people try do in their lives. And they defined

that by saying, you cannot do at least one aspect of your life well.

If you're working, that's more or less all you're doing, you're not taking care

of your family.

If you're trying to take care of your family, you probably aren't having any

real social or recreational time, or work for that matter.

So it takes away the very big, and crucial ways that we define ourselves as

people, and how we value our contribution.

But it's also defined by pain and inflammation. Muscle pain, joint pain, sore

throat, tender lymph nodes, headaches, non-restorative sleep and most

importantly, concentration and cognitive problems that can interfere with your

ability to be as quick as you would like to be.

Slide shown during previous section:

Definition - CFS

>6mo. dibilitating fatigue, unexplained by preexisting illness or psychiatric co

morbidity, and at least 4 of eight symptoms criteria:

post exertional relapse

concentration and cognitive complaints

myalgia

arthralgia

sore throat

painful lymph nodes

new headaches

unrefreshing sleep

There's also a clinical case definition. That was a research case definition.

The clinical case definition was more of a teaching thing, to try to teach

doctors who use this that there is something underneath all of that.

That those are autonomic symptoms.

That those are immune symptoms.

That those are neuro-endocrine symptoms.

Then they cluster those symptoms around the type of underlying system that's

acting badly to cause those symptoms.

This was a clinical case definition made by an international group in Canada,

and I was a member of that group.

I wasn't a member of that first group.

I didn't name this disease. No one blame me.

I was not there. I was not invited.

Slide shown during previous section:

CFS/ME Clinical Case Definition

1 Substantial reduction in activity level due to new onset, persistent fatigue

2 Post exertional malaise

3 Sleep dysfunction

4 Pain - myalgia, headaches

5 Neurologic/Cognitive Manifestations

6 At least one symptom from 2 of the following:

Autonomic manifestations eg. OI, IBS

Neuroendocrine manifestations eg. temperature intolerance, weight change

Immune manifestations eg. tender lymph nodes, sore throat, flu-like symptoms

Link to full report www.iacfs.net

There are overlapping conditions.

About 60% of the people with Chronic Fatigue Syndrome also have Fibromyalgia.

Fibromyalgia is a painful condition, and that's what it is, it's a painful

condition.

It's defined by pain. You poke people in eleven different places, sorry,

eighteen different places

and if a lot of them, or more hurt, then they may meet the case definition.

Slide shown during previous section:

Other overlapping conditions

Fibromyalgia

Gulf War Syndrome (VA CSP 16 fold increased risk of CFS in Gulf War veterans)

Eisen et al Ann Int (?) Med 2005 7.142(11)??1

Multiple Chemical Sensitivity

(plus image of 'Classic 18 Tender Points')

But underneath that is a very complicated cause.

There's a pain ramp up that happens in the spinal cord and brain, sending more

and more and more pain signals up to the pain centre, and even very light, non

painful touch can be very, very painful.

Even.. you've heard people say, even my skin hurts.

Slide shown during previous section:

Fybromyalgia

Based on the 1990 ACR classification guidelines:

Historical feature = widespread (axial) pain of 3 months or more

Physical finding = pain in at least 3 of the 4 body segments + a finding of at

least 11 tender points on digital palpation of 18 designated tender points

No exclusion criteria

(??? et al, 1994; Portenoy et al, 1996; Wall et al, 1994; Wolk (?) M, 2002)

(plus image of 'Classic 18 Tender Points')

Gulf War Illness is something near and dear to my heart, and I know Mac (?

Matt?) cause we both do research in this area.

We have some Gulf War guys in the audience here.

Gulf War Illness can also meet the case definition for Chronic Fatigue Syndrome.

They overlap, and much of our research in Miami is trying to decide if they are

the same or not.

And if they are, you know, if the treatments might be the same.

That's one of the main focuses we have, and we have some really cool studies

going on.

And I want the Gulf War guys to know, that I shipped off those boxes to the

Whittemore Institute yesterday, so anyone who's in my Gulf War study,

is having their XMRV serology and blood testing done very shortly. So I'll be

getting back to you as soon as they tell me. So we'll know if it's truly

overlapping in the same ways.

And then Multiple Chemical Sensitivity is an even more poorly understood,

difficult illness, to have, and a difficult illness to diagnose

One of the issues with Chronic Fatigue Syndrome all along has been the attitude

of physicians. And there have been a number of studies done (Lenny (?) did

one, this is a different one), that looked at the attitudes of doctors who don't

even recognise the illness is real. And it works out about 50/50. And the

doctors that do, generally have a family member who's ill.

Generally speaking their connection's not their speciality or their training or

anything else, it's that they're linked personally to a person with the illness.

Slide shown during previous section:

Attitudes of Physicians

Of 811 GP's 44% did not feel confident making the diagnosis, 41% did not feel

confident treating

More likely to have confidence if they had a friend or family member with CFS,

having more patients with CFS.

Concludes that education emphasising acceptance of CFS as a real entity results

in improved confidence in treatment

(Couldn't read source, ended (April 1))

So, what about viruses?

We found most of the work that's been done on Chronic Fatigue Syndrome has been

on mental illness, and depression, and atypical depression. And the patients

have gotten a bad rap.

And I'm gonna say this in sort of in a funny way.

This is my own personal opinion, that part of the reason that there's so much

psychology work done is that this is a very interesting illness from the

psychologist's point of view. As is any really serious chronic illness.

Patients with HIV have a huge mental health literature.

Patients with renal disease, or renal failure, have a huge mental health

literature.

Because one thing you can really do for people with a chronic disease, is try to

help them live with it, cope with it better, and try to have the best quality of

life that is reasonable.

And so, most of that mental health literature is actually focused on that.

All that Cognitive Behavioural Therapy work and so on is focused on that.

I think where Chronic Fatigue patients got really angry, and I totally

understand, is when some researchers went off on the tangent that this is some

atypical form of some primary mental condition.

And I think we disproved that in 1993 or 4. I mean it was a long, long time ago

that all those endocrine studies came out that showed that basically the illness

goes in the opposite direction from all the neuro-endocrine point of view, than

depression or that sort of thing.

But still, there's been this cloud lying over folks with this illness because we

never came up with a very clear understanding of what the primary cause might

be.

And much of the excitement about this virus, is that it is itself a candidate

for being a primary cause.

So it's a very exciting time.

Slide shown during previous section:

Viruses and CFS/ME

Much of the research here and internationally has examined the role of the

immune system and possible chronic infection in CFS

The viruses studied all have several things in common:

they infect cell of the immune system and the neurologic system;

they are capable of causing latent infects;

they can reactivate under certain conditions

Section 2: Viruses & CFS/ME; WPI & XMRV

The other half of the medical literature was looking at pathophysiology, just

what's wrong. And this group in Miami has from the very first day, actually the

very first group, to look at the immune system as a major mediator of the cause

of this illness. In 1989 we wrote a paper from our first series of patients that

show that the chronic fatigue patients had immune activation and poor antiviral

cell function. We wrote that paper in the Journal of Clinical Microbiology back

at the beginning, very early on, and a couple papers right after by Jay Leevy's

group that say the same thing, and that’s what launched us in this field.

So we've been focused on viruses from the very first day. So what do we know.

The very first day we looked at Epstein-Barr virus and other herpes family

viruses. Epstein-Barr and Cytomegalovirus were the first viruses that were

looked at. Dr. Leevy's paper and my own and others said, what we saw in all

these virus serologies we looked at, when we looked at the antibodies, was EBV

is there, we can't say it's not. There's all kinds of other serology for other

things that didn't pan out. But Epstein-Barr over the years, time after time,

there's been at least a subgroup of patients that looked to have a higher level

of Epstein-Barr virus than they should have. CMV a little less so.

In the 1990s two things happened. First, Elaine DeFreitas and Mike Holmes from

New Zealand both published papers at about the same time, 1991-92, saying that

they saw a retrovirus in chronic fatigue syndrome. And Dr. Holmes paper had all

these beautiful scanning electron micrographs of little budding viruses coming

off of white blood cells that looked for all the world like a retrovirus. And

Elaine DeFreitas who was at the Wistar Institute at the time published a paper

that said she had fairly good evidence that there was a retrovirus.

What happened next was a little complicated, partly from our point of view--we

recruited Elaine down at the University of Miami and she joined our faculty, but

unfortunately she became very ill very shortly after and left. So we never got

to pursue her work which is a shame. I’m sure she’s feeling very good right

now about this new work. The other thing that happened was that the Centers for

Disease Control published a paper and presented at a number of conferences that

they failed to find that retrovirus. And it was a shame because that was how it

was left. There was this positive finding from two different groups, one group

saying absolutely not, and then nothing much went further from there. So we lost

unfortunately that time from then to now. I’ll have to say though, we didn’t

know this virus hadn’t been identified yet. I don’t think it would have been

a rapid thing there, but certainly we would have been further along than we were

now.

The HHV-6 was the second big thing that happened in the middle of the 90s. This

other new virus was discovered, human herpes virus type 6, the virus that also

causes the three day measles, another childhood virus—another herpes family

virus. And it turned out to be reactivated in a whole lot more people than the

Epstein-Barr virus. So this was the first virus that got a lot of credibility as

really being there by all the groups that were looking. And there was some

excellent work, Dharam Ablashi who was the discoverer of the virus, discovered

the virus, Connie Knox, and a private foundation, the HHV-6 foundation, that did

some excellent fundraising and really did some pointed research to drive this

home and push that along to the point where clinical trials had been going on to

try to suppress this virus, with some efficacy. So that was very exciting.

So then we enter this decade and we’ve got enteroviruses. That’s Dr.

Chia’s work, where he did a lot of gastric biopsies and he found coxsackie

virus, which is a whole different family of viruses also very common

reactivated, and he found it in the gut wall with a gastroenterologist who was

biopsying stomach. And they found virus.

So it made us stop and think, well wait a minute, if the immune system is broken

enough that more than one kind of virus is getting out, how are we going to

focus our work so that we’re covering this immune system problem. Instead of

trying to pick off one virus at a time should we maybe be backing up and saying

can we fix the immune system that’s broken and prevent these common viruses

from reactivating.

And then finally we come to this definite landmark paper of October 8th in

Science by the Whittemore ’s group with Judy Mikovits and Vince

Lombardi. It is a very important paper, and the reason why this paper is so

important is that this virus is a really good explanation for why the immune

system is broken, unlike the others. This one would explain why the immune

system is broken. And it is also a really important paper because this virus is

not common. There are very few people that have this virus, and yet most chronic

fatigue patients in their study did have this virus, and so it’s a candidate

virus for causation. And that’s, I think, why everyone’s so darn excited.

I put up this slide because this is going to be videod and someone is going to

read this who’s not here, and I want people to know when I’m using someone

else’s slides. I borrowed these slides from Dan and the Whittemore

foundation. These are the people that work him on this, and even though

I wasn’t part of this particular group, I feel like I’m a member of their

family because I spent a lot of time in Reno when they were first setting up,

and I really admire these people. They’re really very talented. So there at

the Whittemore Insitute...even though Annette Whittemore’s name is

not on this slide, it should be right up there on the top. Annette Whittemore is

the reason why the Whittemore Insitute came to be. Harvey and Annette

are these lovely people who know how to get something done. Their daughter is

very ill, and they realized that they were getting the best possible care

because Dan was

their doctor. And they said how sad it is for people who don’t have access to

such talented doctors. So they established this, the WPI, Whittemore

Institute.

And then in a very targeted way and a very brilliant way, they said this is the

kind of research we want to do what we want to focus on, and they made a team

that could do that. They were absolutely virus hunters, they were looking for

viruses, and they put a team together to find viruses. And they got an excellent

team put together, and by gosh, two years into this work and they have scooped

us off. Good job. So they did a fine job. And they did that with their

colleagues at the NCI, Ruscetti, who’s a very famous virus hunter in

oncology, is one of their senior partners and that whole team there, and then

Bob Silverman at the Cleveland Clinic with Dr. Gupta. These are two people, Dr.

Silverman’s one of the discoverers of XMRV several years ago and he was a

member of the team that went after it. So it’s very impressive work.

---

XMRV Virus Section 3

So what is this virus X-M-R-V? Well, the RV means retrovirus. So that puts it in

a family of viruses, retroviruses, that we actually know quite a bit about. And

the X is xenotropic. M was mouse. This virus started in a mouse. Now

there’s…ya know viruses start somewhere. They’ve got to start somewhere.

Like the HIV virus started in a monkey. It’s a monkey virus that eventually

evolved several hundred years ago into a virus that could infect humans. So we

got this lousy virus, HIV.

XMRV is in its own evolution. And it jumped from mouse to human at some point.

We don’t know when, but probably not in the too terribly distant past. Well,

that doesn’t mean a lot, because in Darwin terms, distant past could be 100

million years, but these guys think like that, the evolutionary biologists. That

wasn’t long ago, a thousand years ago or so. But in this mouse virus, it could

have been in the last century. That’s the sense of it.

About 3-4% of people have this virus and they’re not sick. And that’s

another part of this. So there’s this background population. Now, I’m just

saying that flat out, but you know I gotta tell you that the research on this

virus is only 2 years old. And so, we don’t know very much about it. And

there’s probably regional differences. There might even be continental

differences. We don’t know. There’s been nothing done anywhere else. They

did some studies – originally this virus was found in prostate cancer. So most

of the work was done in that area and there’s two studies: one in Germany and

one in Ireland that failed to find this virus in their patients. Now, whether

they’re using the same technique or it’s not in Germany, it’s not in

Ireland, we don’t know. So, there’s a lot of questions still to be answered

with this virus.

This Science paper was amazing for a number of reasons. First, this team had put

together such strong science that they could go for a Science paper. And for

those of you who aren’t in the land of science, Science is like the Mecca of

publication. If you get your stuff in Science, that’s the best place you could

possibly put them. And they don’t take just anything and they sure, sure, sure

don’t take something unless it’s extremely well done, validated and tested

out. So they took this paper. And if you read this paper, they not only took it,

they put it in Science Express. They thought it was so important, they published

it on a very fast track. And so, that was important.

And if you read the paper, you’ll see that found this virus the first way they

looked. They backed up and looked from a whole different angle. Still found it.

Backed up and looked from another angle. Still found it. Then, in two other

ways, they had five different kinds of ways they looked for this virus. And they

were able to find the virus. So I think that’s why Science was so impressed.

They also used a very big population. They had 100 Chronic Fatigue patients –

101. And they had more than 200 controls. So that’s usually…scientists like

that kind of stuff.

And then, the interesting thing was in this paper, the first 20 patients they

studied were Chronic Fatigue patients that had developed some kind of Cancer.

That’s actually how they got the Cancer guys’ attention, I’m assuming.

Because Dr. ’s got 30 years of stuff in his freezer and dug out

everybody in his whole population that had ever gone on to develop Leukemia or

Lymphoma or any other kind of Cancer. They pulled those out first and that’s

actually where they first found it and that’s what got their interest up. And

then they went back and looked at a bunch of others. The way they looked is very

sophisticated and they found 67% that way. And then they tried to find it in all

these other ways, when they added everything together, they could find the virus

in roughly 95% of the patients using one technique or another, but not

necessarily consistently, no matter what technique they used. But it means that

there’s at least 67% of

people in that Reno cohort and possibly quite a bit more.

So what is this virus? It’s a mouse virus. It was first discovered in 2005. It

was discovered by prostate cancer researchers looking for a virus, viral causes

of Cancer. So they found it in that study in 40% of prostate cancer. Another

group looked and found it in 23%. And so there have been two studies that said:

the virus is in prostate cancer. Other groups though, have not found it - in

Germany or Ireland – so it’s still considered somewhat controversial. It’s

a different strain than the one seen in prostate cancer. It’s not exactly the

same. Okay? I’ve already had patients whose husbands had prostate cancer

thinking that they somehow infected their husband. Oh my God, I gave my husband

prostate cancer. Don’t think that way, okay? It’s a different strain of the

virus. They’re related, they’re closely related. But we don’t know enough

to even pretend to go that far with assumptions.

It’s a virus that doesn’t have a lot of mutations. And what that means to

the virology world is that it doesn’t change very much, it’s not shifting

around, there’s not a whole bunch of different kinds of it. Like there is with

HIV, where within a few weeks of applying an antiviral, the HIV virus can mutate

away and escape and go off and do its own thing. So this is a pretty stable

virus. That bodes well, particularly for vaccine work. That bodes extremely

well. We don’t know what that means to the antivirals yet. It just depends on

how much replication is going on.

Why does it fit into Chronic Fatigue? Well, there’s a lot of good reasons why

it fits in to Chronic Fatigue. Those of you who live and breathe this stuff

might have heard me talk about natural killer cells a little bit. ((laughs)) NKs

are really broken in Chronic Fatigue Syndrome and natural killer cells are part

of your defense that prevents latent viruses from reactivating. And they really,

really don’t work well in Chronic Fatigue Syndrome. And our group has done 20

years of work to try and figure out why – and we know why. And we also extend

that to say: these natural killer cells that don’t work are closely related to

a different cell, cytotoxic T-cells. And they don’t work either and between

the two of them, that is your antiviral, latent viral reactivation system. Both

of the systems are broken.

So, enter a virus that infects and affects natural killer cell function and

that’s this one. And infects and affects T-cells, cytotoxic T-cells. That’s

this one. So we’re kind of keen, we don’t know for sure, I mean this so

early in the work, we’ve gone all of three weeks since that paper came out.

There’s going to be a lot of work to be done. But it would make a lot of

sense, a good hypothesis to construct if this virus is in there mucking up cell

function, and that would make a lot of sense to what’s going on.

It also is a virus that can infect tissues that aren’t white blood cells. And

we’ve always thought: something like that has to go on in Chronic Fatigue

Syndrome because you all have some neuro-inflammation. Your brain has a low

grade level of inflammation. And you have some inflammation in the tissues that

make hormones, particularly the hypothalamic-pituitary axis. And this is a virus

that has some tropism or infects that type of tissue. So it starts to make the

whole picture come together. Now we don’t know enough about this virus’s

tropism or what stuff it likes to infect. This is just sort of the first look

and some of this may change as we get more sophisticated and look with better

ways. But the sense is this virus, if it’s acting like its cousin virus HIV

that likes to infect those kinds of tissues, that it’s going to have receptors

that let it into other places too. Anyway, I think it fits well and I’m very

excited about that fit.

And 4

When we talk about latent viruses, this is what we’re talking about. The guy

on the top is a quiet little white blood cell hanging out doing nothing because

no one has asked him, it doesn’t have a job yet. If it becomes activated,

it’s because something floated into the system, some antigen, some bug that

it’s supposed to respond to. And in our systems we have hundreds of millions

of these little quiet cells and each individual cell only knows its one little

job.

Now this one’s for Epstein Barr, that one’s for Staph, and that one is for

some other bug. If that bug comes into the system, then that cell is the one

that gets activated. And if it had hidden inside it, in its DNA like over there,

if it has inside it this little piece of virus fragment, sitting in that DNA,

that cell is turned on to make all of its stuff it knows how to make. It got

activated. It’s going to make cytokines, it’s going to make interleukin 2,

it’s going to make ?? , oh and by the way, it’s going to make that sneaky

little virus that was tucked into its DNA too. And that’s what happens.

These latent infections just sit around doing nothing until that cell is

activated and then boom, they start making virus stuff. Retroviruses are funny

because we’re just chock full of them. We have little bits and pieces of

retrovirus all in our DNA. Talk about evolution, our great, great, great, great,

great, great, great grandfathers got infected with some little piece of

something, maybe a chunk from a mouse back then. But it’s not a whole virus.

They have just little bits and pieces, of bust up pieces of retrovirus tucked in

the DNA. We think it’s an important part of the way that we evolved. That we

borrow DNA from other species this way and we transfer things around. If viruses

carried little pieces of information into the genome back then. And some of it

was bad and that didn’t work out. And some of it was good and it carried on or

it was neutral and it carried on.

But there are some retroviruses that can be carried generation to generation as

a whole and complete virus tucked into that DNA or rather enough DNA to make a

whole and complete virus when it’s turned on. And this is one of those

retroviruses. It can be transferred generation to generation or what’s called

vertical transmission, mother or father to child through the DNA. So we don’t

know if there’s 3 or 4% of background. There’s just people who have vertical

transmission or if there’s some way that you can infect people back and forth

in life. We don’t know that at all, okay?

But we do know that this virus is one of the ones that is vertically

transmitted. We know that from the mouse data. So it can be transmitted

vertically. So the question is if you have children, do your children

necessarily have it? And the answer is maybe yes or maybe not. First off,

there’s two parents not one. And each only give half of the DNA, yeah, right?

So in any given child, there’s only one chance in four that you can pass on

any particular piece of DNA on a good day. So you don’t worry too much about

kids flat out that way. And then you say: And oh, by the way in their life, they

have to come across the thing that activates the virus and turns this whole mess

on. And so there’s a whole lot of reasons not to get all worried about…I

mean I’m not saying it couldn’t happen to your children…Of course it’s

conceivable. But what’s exciting right now is we’re getting this, we’re

getting the understanding of it, and we’ll

probably, knock on wood, that we will be to the position where we’re actually

intervening effectively before it becomes a bigger worry. But, um, I don’t

know about kids. I’m saying it is a vertically transmitted virus.

We don’t know if it’s sexually transmitted. I will say that there are

sexually transmitted retroviruses. We know HIV is, obviously, is a sexually

transmitted retrovirus. But, there’s no…you’d think in 25 years, we would

have seen massive numbers of spousal pairs. And we have not. You occasionally

do, occasionally we do see a spousal pair. It happens. But almost always those

people both had acute infection at the same time at the onset and it’s really

unclear if it was transmission between the two of them or if they had some other

thing happen that kicked off the whole, the whole thing. And you see household

Chronic Fatigue. I mean I do see mother-daughter, father-daughter, father-son,

whatever…I’ve seen it. But, in my clinical practice in the 25 years or so,

it’s not very common. It doesn’t happen a lot.

So, the next slide. This virus is not HIV. A lot of people panicked when they

heard this. This virus really is not HIV. It’s in the same family, but it’s

a distant, distant cousin…very very distant. And it’s not infecting or

affecting the same cells. So, it’s not doing the same immunologic thing that

HIV does. Okay?

There are also other retroviruses that don’t do anything that we know about.

There’s a virus called HTLV-2 that I have studied myself in the past, and many

others have, and it’s just sitting around doing nothing. It’s

really…it’s vertically transmitted, it even replicates, and it doesn’t

cause much in the way of illness. So, that doesn’t necessarily mean that just

because you find a retrovirus, it’s definitely the deal. And not every

retrovirus is big and bad and ugly. There’s another virus called HTLV-1

that’s vertically transmitted and does cause an illness. And it causes a

neurologic illness. And so, we have different bugs, different things.

HIV is a retrovirus and there’s at least 20 or more drugs directed at HIV. So,

will those drugs work to control this virus? That is definitely the big question

of the day. And the first thing to say is: some of them probably will. And the

second thing to say is, but not all of them…you couldn’t just pick a random

one and try it.

This one’s to show you mouse going to people…that basically it started out

way up there as a mouse thing. Mice learned to live with it. They don’t have a

receptor that allows this virus to become a big bad deal. So, mice just sit

around for generations and generations of mice being a reservoir of virus, but

not actually getting sick from the virus. But then the virus shifted and it

became capable of jumping from species to human.

So, this was the study. They had in their freezers samples from people that

weren’t from their cohort. So, these were not just Reno samples. There were

samples from Florida, from California, from North Carolina, and other places.

Everyone in their repository had a Chronic Fatigue diagnosis. The mean age was

55. There was two thirds women. They had this large control sample. They

looked…and they looked at these patients, out of 101 patients, and they looked

at the DNA, the sequences of the virus in the DNA. It’s really a sophisticated

way to look and they found it in 67% and in 3.75% of the 320 controls.

Now of the negative, these 33 negatives, they went on and looked in other ways.

And they found 19 of those had antibody in their plasma, so that was more than

half of those negatives. But this is the big number: 30 of the negatives had

virus they could identify by taking the serum of those cells, the serum from the

plasma, and infecting a cell line and then growing the virus in that cell line.

So they could transfer from the plasma, virus to the cell line. Now that has a

lot of implications and it’s certainly the reason why, in part, the CDC, the

NIH, and others that really care about the blood industry are looking long and

hard at this. They found the virus, a transmissible virus, in the plasma and

they were able to infect cell lines. So it is suggestive of an infective

component, at least in the blood. And then there were other ways, so they worked

out that they were able to find 99 of the 101 patients in that way.

Now think about that for a minute. We define an illness by a bunch of symptoms.

Now, I’ll say Dr. is a really fine doctor, and I’m quite certain

that he’s not misdiagnosing Chronic Fatigue Syndrome. He’s really splendid.

So, it could be that he has a really clean, tight population of folks in his

freezer. But I would say, I think I’m pretty damn good, and I think if I

pulled out stuff from my freezer, there might be a couple of MSs in there or

something else that evolved down the line. I mean, I’m not sure. But it’s

pretty impressive that out of 101 CFS defined by clinical case definition or a

research case definition that they found 99 with virus. And if this is the case,

that’s pretty exciting. It’s pretty impressive. And, oh, by the way, we have

a biomarker. Not a small deal. A biomarker – the virus itself. No better

biomarker than something that’s clearly, tightly associated with an illness.

Section 5 – Antibodies, What we don’t know, Cancer

Antibodies

[Question from audience, inaudible]

Oh that’s a really good question. She asked: " If there’s antibodies why

don’t the antibodies kill it? " That’s a very good question and one that dogs

the vaccine-development people in HIV all these years. The reason we don’t

have an HIV vaccine yet is that antibodies don’t kill HIV, you need cytotoxic

T-cells to kill HIV. So all those vaccines for HIV have been trying to get the

cytotoxic T-cell lines all geared up and ready to go and not focus on the

antibodies. The antibodies don’t do it. Whereas for other viruses the

antibodies are great for it. I mean all those childhood vaccines you got were

just trying to build antibodies for all those years. So there are some viruses

that just the human body doesn’t make a killing, lethal antibody to attach to

that virus. So we don’t know this virus well enough. I don’t know, there

might be an antibody that kills this virus. It’s only been a few years. They

haven’t had a chance to look very

hard. The other thing disturbing on that other one was only half the people

they looked at had antibodies, but they had the virus. So antibodies are

probably not going to be our world’s best blood-test for this.

Judy Mikovits renamed the illness, I’m not sure this is going to stick, but

she called it XAND. XMRV Associated Neuroimmune Diseases. The reason why I

don’t think it’s going to stick is I don’t think the “M†is going to

stick very long. I think as soon as this virus is clearly shown to be a human

virus, they are not going to call it a mouse virus any more, and they’re going

to rename this virus, and then we’ll be renaming again. So I’m not leaping

to embrace the new name, but I will embrace any name that’s not Chronic

Fatigue Syndrome! [Applause]

Slide: XMRV Associated Neuroimmune Diseases (XAND)

Potential Candidates:

• Atypical MS: 3/3 positive for XMRV ENV protein and gag DNA

• Fibromyalgia: 12/20 (60%) positive for XMRV gag DNA

• Autism: 6/15 (40%) positive for XMRV gag DNA

4/7 (57%) positive for serum antibody to XMRV Env

• Gulf War Illness: Not tested

Samples were taken from family members of XMRV positive CFS

subjects with these neuroimmune diseases.

This is also stuff they showed just last week, and this is not published data.

And these are not going to be very representative because these are family

members of CFS patients, who happen to have MS, fibromyalgia, autism. And in

family members of CFS patients who had these other conditions they found XMRV in

that family member. So there are lots of questions. This is the first paper. The

paper is very exciting. The next step is to validate the paper. The very next

step. And this is going to be difficult because what did I tell you about the

prostate work? Two of them said yes, and two of them said no. Now if you talk to

the guys who said yes, they’ll say the guys that said no didn’t use the same

method to look. That’s science! We do this all the time. We get into big

quibbles over method. Method, method, method!

Already I have a conference call with the CDC on Monday because they want their

samples. The guy at NYU wants their samples. The guy at Hopkins wants their

samples. I mean everybody knows that I have a freezer full of samples and my

reaction is: Oh my God, what method would you apply? I don’t want to be the

one that had the bad method. I don’t want my name on the paper that didn’t

use the right tool! So, the first step I think is to get all the people trying

to do this together and use the same method. And that’s absolutely necessary.

And if you see some negative papers coming out, don’t be discouraged. It’s

going to happen. There are going to be some negative papers. People really jump

to do this. And the method is not that easy, and getting the right bits and

pieces you need together, it’s not: read the paper and then go do it.

Things we don’t know.

What cell types are infected? We know for sure that NK-cells are and other white

blood cells are. We know that there is some neurotropism [affinity for nervous

tissue] from this virus from the mouse studies. But we don’t know every kind

of cell type that could be infected and what’s infected in humans.

How is it transmitted? A critical question. Certainly the blood bank industry

has jumped right in and are going to try to see if this is a worry there because

they have freezers full of samples they can go back and survey for any positive,

and then actually have recipients, and they can see if there are any recipients

that are positive. So they’ll be able to test that theory I think very quickly

and very efficiently.

What is the immune response that controls this virus? You asked that question:

would antibodies do it? And the answer is (that's a great question) the

antibodies might do it. Cells might do it. It might be that we have to repair

these cells and then they can do it. But those are good questions. We don’t

know with this virus what the answer is. But we do have a much better sense of

what retroviruses are after the last 20 years of HIV work. We really do. I mean

I go to the HIV meetings and I go to the CFS meetings. Let me tell you the

difference. Reno, and this is a pretty big meeting last year, I think they had

100 and maybe 200 investigators, and that was the whole world, the Japanese were

there, the Europeans were there and pretty much it’s a who’s who of who does

this work and there was 200 of us. And the HIV meetings, I’ve been to meetings

where 18,000 people came [gasps from audience]. And that’s the kind of brain

power that was being

directed.

Now the other thing about the HIV guys is that they are kind of bored, don’t

have anything to do, patients are doing well, [laughter] science is a little

dry, not a lot of grants. Cool! We’re going to suck some of those guys right

into our field now. This is going to be really, really good. We’ve been

waiting for a flush of brilliant new people, and I think we are going to see a

flush of brilliant new people come into our field if this holds up, there’s

going to be a lot of good interest.

Cancer

Does this virus alter the risk for cancer? Now it’s a question that has been

left unanswered to you and every single one of my patients has asked me this

question. Do I have an increased risk of cancer? My gut reaction is yes

probably, because the cells that are your cancer-prevention cells are part of

what’s broken or partially broken in this illness. So you always hear me

talking about anything you can do, [e.g.] antioxidants, to try to help you any

way you can to boost up your own tumor-defense systems. And these cells in

particular. But here we are 25 years into this illness and we do not to date

have a natural history study that is longer than 3 years. No one has yet

answered for you the question that needs to be answered. Part of my motivation

to put together these clinics with Hannah, these Chronic Fatigue clinics, is

that we were going to use this big common database and if we really can get a

bunch of clinics all linked up together using the

same database we’re going to have a natural history study finally. Because

you have to do it yourself. That’s how it works in this field. We actually

don’t have that information for you.

Can we develop Immune-based therapies? I and [Dr] Mikovits have been working on

immune-based therapies for years. We did a really cool one years ago with cell

extension. Some of you were in that study and some of you got really big

impressive results when we enhanced your cytotoxic T-cells and your natural

killer cells. You got good clinical improvement.

And 6

And here’s the real compelling question: will antivirals work? This is a virus

that’s sort of coming in to a white blood cell and it’s hunting for its

receptor. And then it’s going to attach to this cell. This is a retrovirus

attaching to the cell. Now in this virus, we don’t know what that receptor is

yet in human. We actually sort of have an idea from the mouse work, but we

don’t know for sure. But there’s an attachment step. And then the virus

enters the cell. It fuses to the cell. In HIV there’s these entry inhibitors

and fusion inhibitors that prevent that so there are potential therapies if it

were the same receptor. I kind of doubt it. I don’t think we’ll be using

those particular HIV drugs.

Then it gets into the cell and when it gets into the cell, it dumps its RNA into

the cell. It pokes a little hole and the virus comes in. And then that RNA comes

out. And we’re DNA, not RNA. The nucleus of our cells is DNA, so it has to be

turned into DNA. And to do that, it uses an enzyme called reverse transcriptase

and that turns the (see I knew before that thing before it told me. I am smart).

Anyway, it turns RNA into DNA and that is a wonderful target for this

virus…the reverse transcriptase inhibitors…because then the DNA can

integrate into the cell. Now we have integrase integration inhibitors also…in

HIV…integrase inhibitors. But they are fairly selective for HIV. I don’t

know that they would be effective in another retrovirus.

And then, when the cell is activated and its DNA starts making stuff like this,

it has to be…it makes these great big long proteins and those proteins have to

be cleaved into little pieces (see I’m sinking here). And that’s the

protease inhibitor line in HIV, the proteases that cleave are inhibited and that

prevents that piece from being torn up. And then all these bits and pieces

assemble themselves over on the cell wall and they bud off – BOP – and

there’s a virus. And that’s how viruses are made.

So, we have entry inhibitors, we have reverse transcriptase inhibitors, we have

integrase inhibitors, we have protease inhibitors. And then all those put

together is the whole repertoire of drugs that have been developed over the last

20 years or so for HIV.

But, be it known that there are literally thousands of compounds in the

pharmaceutical companies’ shelves that they developed for HIV that weren’t

as good as things for HIV that approved that might be the very perfect thing for

this virus. So, we’re not starting from scratch here with this virus – at

all! The other thing about this virus, and this is just from what Dr. Coffin

said at the Chronic Fatigue meeting on Friday (I’m not a retrovirologist as

brilliant as these guys) but I can parrot them pretty well. Dr. Coffin said –

because this virus doesn’t seem to mutate very much, it’s a great target for

vaccine trials.

And when you ask - what about antibodies? – if we vaccinated people to this

virus that already had the virus, we could goose up their immune response to

this particular virus. That’s what they’re doing in HIV trials, they

vaccinate infected people. So you might suppress the virus with an antiviral and

then goose up the immune system with vaccines, so it could really work hard on

this virus and then reduce it. So you could start postulating. Isn’t it fun to

be able to postulate therapies…I mean, it’s great. I’m loving this. I’m

lying awake at night thinking of all these things. It’s like – oooh,we could

do this – oooh, we could do that. Good stuff. I know, I know, I’m an

immunologist, what can I say?

Of course one of the things I think about is immunomodulators – drugs that

would either quiet immune activation or enhance cell function are very

appropriate. Okay, so what’s already out there? Well, Ampligen, Ampligen’s

an interesting drug. And they actually showed – they had 8 patients that had

Ampligen data – that they showed at the CFSAC meeting that Dan showed. And it

had a mixed result. In some cases, Ampligen was very effective in suppressing

this virus, and in some cases it was not – in those 8 patients. That’s not

very many. But Ampligen sounds kind of promising because it’s an antiviral

that’s an immunomodulator that enhances natural killer cells and cytotoxic

T-cell function. It’s even more intriguing than before in my mind, I think

Ampligen’s got some real potential.

Immunovir (Isoprinosine) – some of my patients are on this medication. It’s

only had phase 2 trials, it hasn’t had phase 3 trials. But it’s more or less

a nutraceutical, it’s an amino acid. But it is also an NK cell enhancer and a

cytotoxic T-cell enhancer that may have some antiviral effect.

This cell therapy – I referred to this ex-vivo cell therapy – some of you

were in this study – It was in 1993 or…it was 1993. Well we took a lymph

node from a patient and we grew the cells in a laboratory and we made literally

a transfusion of white blood cells. Max did that. He was busy, busy transfusing

my patients with white blood cells – their own white blood cells. But in the

test, in the laboratory, we had grown them, fixed sort of what was broken about

them, and then we got some very very nice clinical responses in that Phase 1,

that study that never got to go to a Phase 2 study for lack of funding. And then

finally, this makes cytokines that are either directly antiviral or immune

enhancing more interesting.

The nutraceuticals, they have less work done. Omega-3s are anti-inflammatory,

the mushroom extracts that the Japanese use to enhance natural killer cell

function, but these aren’t studies that had placebo control data and looked

promising. CoQ10 at roughly 100 twice a day – that was really anti-fatiguing

and enhanced cell functions. TNF inhibitors, we have a couple few patients on

TNF inhibitors and I’m seeing some nice responses if they’re cytokines are

way wacked out and they’re super revved up.

That’s a natural killer cell, the little guy killing that target cell.

That’s an Epstein Barr virus infected target. And there’s that little white

blood cell doing its job. That’s what we’re trying to do. So the white blood

cells infected with virus and you want these cells to go in there and kill that

cell. So, the other question with this is: okay you’ve got one virus, but what

if you’ve got this virus plus a couple of other viruses? What’s the role of

all these viruses all together? What about HHV-6, EBV, enteroviruses, and this

virus. If we say that all these viruses are doing their work together, it might

be necessary to treat more than one virus. It might be necessary to design a

study that has the retrovirus piece and a Herpes virus piece because sometimes

viruses lend each other machinery to make their infections more potent and

damaging.

Section 7: What’s Next in Research?

(Slide – What happens next?)

What happens next is very clear, research.

Dirty word but the most important word in the whole game. Gotta know that

research has to happen and it is the research that gives us effective therapy.

I started HIV in 1983, is when I finished my residency. And so I started right

here at the University of Miami and I started right in the HIV program before we

knew the name of that bug. And in 1984, the bug was named, and in 1988 the first

anti-viral was tried, it was a little bit helpful but it wasn’t all that

effective. In 1994 we had three drug combinations that just kicked butt. In the

time between 1983 and 1994 I lost 1000 patients. It was devastating, I was

emotionally a wreck every time I went to clinic. And now I am going over to my

HIV clinic at the VA and I am taking care of blood pressure, I am taking care of

hypertension and cholesterol and the usual stuff. And you know, HIV sometimes

does it’s dirty deed which is to say to make people a little more prone to

cancer, sometimes we get some cancers, but most of my HIV guys are really

healthy.

I got into a little trouble in the New York Times for saying this, did anyone

see me in that Times? I said my HIV guys are hale and hardy and my Chronic

Fatigue patients are not, they are not. And that’s true, but I am very

privileged to have been a doctor caring for all those people and then being

there when the time happened when these things changed. You know, there I was an

HIV doctor, dying patients, going to funerals, and taking my patients, doing

rounds of hospice on my way to rounds on the regular wards and then I was there

and in a matter of a few months I had patients that went from 80 pounds to 180

pounds.

And I got guys that I take care of now and I remember them from when they were

80 pounds. I have one guy that played basketball six hours a day, he’s the

most muscle bound handsome guy you ever saw and he was nothing but bones and

that’s because I stuck it out and I feel really privileged that I got to be

their doctor and see them all the way through but that’s how I feel about

Chronic Fatigue Syndrome right now. I mean, I’ve paid my dues. You guys have

certainly paid worse dues than I’ve had to pay on this. But I’ve paid my

dues, I’ve had the privilege of being your doctor and watching you bear

through all of this. And I really think we’re at this point now where I am

going to get to be there during this wonderful transition from really sick to

hale and hearty and that’s what I am really looking forward to. So we’re

going to do that, right? (applause!).

So what’s next with research?

(Slide - What Happens next?)

And the research is going to be a lot of different kinds of research. We’re

going to have to do basic science research to understand this virus. The first

step is just to validate that study that was October 8th in Science which is

already going on, but there are probably ten other studies going on. Now I am

going to do that too. To see how far it extends. Is it in Gulf War Illness? Is

it in Fibromyalgia? Is it in autism? That’s a really interesting question. I

mean for my nephew’s sake, I really hope it’s true. And so on. There are

some real possibilities here. This virus has been a sneaky virus messing people

up in more than one way for a while, or it might just be a Chronic Fatigue/ME

virus.

The next step is in culture - what drugs work? What drugs that we already have

that we can quickly roll out in clinical trials work? Meanwhile, in the back,

what other drugs are on the shelf that might be even better than the one that

are already out there for HIV? And we’ll be able to do those phase one and

phase two trials very quickly. They could happen very, very quickly. There’s a

lot of motivation here. You guys are sick but there’s also one million of you,

you’re a hell of a market. And that’s just the United States.

So if we have a biomarker that we can diagnose with, which is a huge step

forward and we have a treatment, a potential treatment, then I think you’ll

have the attention of Burroughs-Wellcome, and Roch and Abbott and all the

companies that have anti-retrovirals as their primary deal. The

immuno-modulators, don’t leave us immunologists out of the big push forward. I

think immuno-modulators may well have a role.

Sub-grouping patients by different things, could be, here’s a big make

believe, but what if it is autism? What if you get a virus in your head when

you’re 18 months old? What if you activate a virus that was in your genome,

vertical transmission when your 18 months old, 12 months old, and what’s

vulnerable at that moment in your life is your brain. So, there’s a lot of

work to do down that line.

Then there’s phase one, two, three trials; the subgroups; co-infection work;

and then finally, basically, what’s our long term plan? How are we going to

treat people at different stages of this illness for how long, with what, and so

on?

But hey, we can have some marching orders here. These are things we know how to

do. We’re good at this. This is what’s so much fun is that so many people

know how to do this kind of work. They’re going to be excited to get into it.

So Phase One are those little small trials where we just try it out, there’s

no placebo. It’s mostly a safety study but also an efficacy study. Phase Two

is the next step when you do a bigger study, usually 30-50 people in each arm

and there’s a placebo involved.

(Slide – Clinical Trials)

Phase Three is when you saw Phase Two looked pretty good so you go for it and

you get a lot of money together and you do studies on 400 to 500 people in each

arm.

We have one other little advantage right now, and I hope it will hold up but

right now the FDA perceives Chronic Fatigue Syndrome as an Orphan Disease, an

Orphan Drug Disease. That’s partly (determined) by how many people have it and

they’re saying because less than 200,000 people have been identified with it,

and that’s true, only 15% of patients have been diagnosed, that we will fit

under the Orphan Drug Guidelines, which lets things move a little bit faster,

you can get things out to market without quite as many steps. That would be

good.

(Slide – One do-all design)

This is just one kind of design I threw up here just to show you what people

would think about. I thought this one up and no one’s going to believe me but

I think it’s a great idea which would be an anti-(retro)viral (Group A) on the

top; an anti-(retro)viral with an anti herpes family drug on the middle (Group

C); just the anti-herpes viral drug on another arm (Group ; and then a placebo

on the fourth (Group D). So you’d actually do four arms at once and answer all

the questions in one fell swoop.

There’s a neat anti-herpes family anti-viral that is in a phase three trial

that’s very low toxicity that a company has in California. They just presented

at the infectious disease meeting, their infectious mononucleosis data and it

was really good. So it might be a drug that’s less toxic than the one we

already have (from audience – What drug is it?). It doesn’t have a name yet,

it’s still all numbers. I’ll tell you about it. It’s exciting. So we’ll

see. There’s all kinds of things to think about.

(Slide – What would that take?)

So what is that going to take?

It’s going to take basic scientists and clinical scientists that are working

together doing the in vitro work. Funding. Interested companies that want to do

the big clinical trials. And ultimately, an NIH clinical trials group to work

together to make it happen.

How fast it happens all depends on the money. It always about the money.

Section 8 – Research Funding & Advocacy

(Slide – Sections Overview)

When you get down to it, the reason why this happened this fast is the

Whittemore’s put their own money into it. They didn’t go through the NIH.

Slide – The Importance of Philanthropy

    * This Huge finding was funded primarily through private donations

    * Private donations give the investigator the flexibility to jump on a

finding this important, and not wait the 12 to 18 months required for NIH grant

preparation, submission, review and funding (Though, believe me that this is

happening too!)

I’ve been to their fundraisers, They put on these glorious fundraisers, they

can raise a million dollars in an evening. It’s amazing. And they raised

enough money and put some people together and in two years they did this work,

they didn’t have to wait for a review process and wait for the cycle, cycle,

cycle.

Right now if I wrote a grant today to do this it would be submitted in January,

it would be reviewed in March, it would go to council in July, it would be

funded in September and I would get to start a year from now. So private money

sometimes is the best money, particularly when you’re on the edge of something

really, really big like this.

So certainly, one of the biggest things that going to happen right now is fund

raising, it is going to be private foundation type fund raising. It’s terribly

important. In addition to doing the stuff we’re going to do with the NIH and

all of the other funding from federal agencies that do this kind of thing.

It’s going to be everybody working together.

So, philanthropy is really important. And I put this slide up, not just for the

people in the room but because we’re putting this video on the web and I am

hoping it’s going to reach a lot of voices.

Slide – Importance of Philanthropy

    * If you were waiting to donate, now is the time – the difference could

be the difference of years until effective therapy strategies are worked out and

in place.

    * Consider:

    * The University of Miami Morton Fund, in memory of Morton who died

as a result of CFS

    * The IACFS/ME research fund

    * The Whittemore- Institute

    * The CAA research fund

    * The ME/CFS Pocket Money Research Fund at www.pocketmoneyfund.org

This is the time to be philanthropic in this disease. This is your moment. This

is the time your dollar makes the biggest possible difference. Hear me say that

never has there been a more critical time to invest your philanthropic dollar in

this disease. We wouldn’t want to you to take away from some other diseases

but do it anyway. Jump Ship. Come on over because we really need this money

right now to do this incredibly important work.

And we are doing the other important work that it takes to get grants through

the more traditional avenues but that will take time. And time that you guys are

out of. You are ready for this to happen. I know you are. Everyone is begging me

for the next step and we don’t have it because we need to do the science.

So what kinds of places might you put your money?

Slide - Importance of Philanthropy

    * University of Miami Morton Gift Fund

    * http://www6.miami.edu/umgiving

    * Specify the Morton Gift Fund

    * CFIDS Association

    * Whittemore Institute

    * ME/CFS Pocket Money Research Fund www.pocketmoneyfund.org

Well, I’m going to make a pitch for University of Miami right here and the

Morton Fund (https://www6.miami.edu/campaign/gift...g.html?unit=16). Beth

Goldberg who put all of this together with the help of Pandora

(http://www.pandoranet.info/) and Dan Moricoli. We have a fund called the Morton

Fund, it’s named after a young man that died of Chronic Fatigue related

complications some years back and has been my main research donation tool here

at the University of Miami. There’s also the Whittemore- Institute;

the CFIDS Association has an excellent donation account; the IACFS/ME which is

the professional group that I was president of not very long ago. And then Dan

just put together this pocket fund web-site. A lot of different ways you could

give where it would make a difference. But do think about that.

I didn’t put on the international links. I meant to do a little research

before I did this but because this is videoed and it will be international I

would ask people internationally to think about their own foundations,

I know New Zealand has a terrific group, the ANZMES group

(http://www.anzmes.org.nz/); Excellent groups in England and Ireland; ME Trust

(http://www.imet.ie/) and others. Barcelona has a fabulous group. There are a

lot of different places where one can put their donation dollars and make a big

difference. And it would be a really good year to make that your plan.

Advocacy

Slide – The Importance of Advocacy

    * No better time than now to let your government (know) that 20 years of

trivializing this devastating illness has stopped and it is payback time.

    * Demand clinical trials

    * Demand serious research funding, set aside dollars big enough to deal

with an illness that has hurt 1 million Americans

    * Demand private disability companies retract the mental illness

decisions and payback your lost income

In addition to fund raising, now is an awful good moment you advocates. This is

a good time and you are all advocates for your own illness. No better time than

now because you have a passionate story. You’ve spent 20 years with an illness

that’s been basically “blown off†(Audience – 30!). A Long time. So, you

know you are standing in a position where people should feel a little

embarrassed, you know a lot embarrassed, a whole lot embarrassed. Your

government should feel like they have a true obligation. I will say that at that

CFSAC meeting last Thursday and Friday we were getting, people were hearing us.

I think we were really being heard. And certainly, take that all the way; push

it; go to your congress people, OK. You can only push the NIH, they have their

budget and they are told to do every – they have one pot and everybody wants

it and they really can’t be told to spend it this way or that, they end up

having to divvy up one way.

You go to congress, they can actually put aside money and there is one really

important tool they have. There is something called the Office of

Congressionally Mandated Research. This is an Army office. It comes out of the

DOD budget, a very healthy budget one might say. The Office of Congressionally

Mandated Research and that is absolutely the place where advocacy can put real

committed dollars to an illness. Gulf War Illness has that, in fact my research

right now is funded through the DOD, Gulf War Illness, through the Office of

Congressionally Mandated Research. They are wonderful people, they are very

professional, they know how to do peer review properly, they know how to get

money into the hands of people who will really spent it in a… and boy do they

watch how you spend it. The Army - I’ve never had so much oversight in my

budget in my life.

So, sitting in your seat – Are you excited? Yeah, you should be! It is damn

exciting! This is great! This is the good stuff; this is what you’ve been

waiting for (lots of applause – around the world!). I mean really – Yea!

Reply With Quote

And 9

So, there are some issues here. That blood test only identified 67% so if I

ordered a blood test on you right now and it was negative, what would happen to

your soul? You know, and yet it might not really be negative, in fact it’s got

a one chance in three of being wrong. The blood test that we don’t have yet

that we will have very shortly, those tests are going to be improved on.

When the first HIV blood test came out it wasn’t any good either. You know, it

went through stages and stages and stages before we got a really good one.

Don’t rush to get the test. Why, because you’re not going to act on that

test quite yet. The knowledge of being positive is not going to give you an anti

viral prescription from anyone right now because we don’t know which one to

give and if it’s safe or if it’s toxic. The HIV drugs are not been gentle,

OK, and you guys are really tender. So, if you knew your status today it really

wouldn’t change anything.

If they are right 99% of you are positive. And if they are wrong then 95% of you

are positive.

So when? Soon, really soon. But you wouldn’t be able to bear the false

negative right now so be careful OK. There are kits already out there, they want

cash and there’s no reimbursement from your insurance provider yet. I was

talking to this great scientist at the VA and he said, you know, my lab develops

tests. That’s what we do. What’s wrong with the tests you got? Oh, I could

fix that and he got all jazzed and I’m thinking, damn, get another guy in the

field and you know, and he’s fixed your test, that’s great. So these people,

they’re already out there and they know how to do it and tests will improve.

If you don’t have this virus – what if you didn’t. Well, you know,

that’s good news too because that puts you in a different group and we know

not to do all that toxic stuff to you. So that’s an important thing to do too.

So don’t be discouraged even if you’re negative.

We talked about these other people that might also actually be infected. We

don’t know. These are just people we are going to be looking at. The Gulf War

Illness group I’m desperate to see right away because it could change the

whole direction of that work and they have a fair amount of money to do that

work.

So the conclusion, it really is a big thing. It’s a big thing. You should be

very excited. It’s a very hopeful thing. Yeah, the research is already

underway, more to come. The more we can get funded the more focused and intense

we will be in getting this work done as quickly as possible. That work we were

already doing plays right into this. All the genomics work and all the

immunology work. That is all critical to the better understanding of this

illness and how this virus plays into it.

Those of you that are in my good day bad day study, it’s nice because we’ve

got your stuff already in the freezer and we’ll be looking at this virus as

quickly as we can get access to the assay. That study, that’s a really

important study. It looks at people in relatively better times and worse times

and we’ll know if viral load is causing that. If there’s anything about this

virus. We’re already looking at all the immune parameters and endocrine

parameters and everything under sun. But we’re trying to understand what

mediates relapse.

There are people in this room that have been in my genomics study where we put

people on a bike and made them sick on purpose and then watched why they got

sick. That was a heroic thing to do, we appreciate it, we’ve learned a

tremendous amount from that study. We want to continue doing that study. We’re

fundraising to do the last of the chronic fatigue group. We’re going to run 15

more chronic fatigue patients and then we ran out of money. I’m looking to

finish that study. You can be sure we’ll look at viral expression now that we

know that we should be looking for viral expression.

So, all these thing are important. They all tie together,

Section 12

Taking care of yourself

(Question from audience) What is going to give us most bang for our buck right

now. If we’ve got $50…

(Answer) Morton Fund, darling. No seriously, Morton Fund really, really needs

your money. We’re down to the last dollar. The reason why were able to do the

genomic study is because of the Morton Fund. I was only allowed to do it on the

Gulf War patients and I was able to take just $50,000 and do literally about a

half a million dollars worth of research because I tagged it onto another study

that was well funded.

(Question from the audience) What do you think is the most important thing that

we could be doing for ourselves?

(Answer) There’s some very important things that you can do for yourselves,

OK. And remember that the issues with chronic fatigue syndrome are that sleep is

non-restorative, the immune system is over activated and not working and viruses

reactivate, the endocrine system is acting a little funky and is a little

disregulated and your autonomic nervous system which controls your blood

pressure and pulse and all that is some sort of seesaw yo-yo thing that goes up

and down. And the combination of all that makes you ill.

First you need to , well it’s so simple, eat right. The rule of exercise –

exercise makes you relapse but you can exercise up to the point of relapse and

you’re better than not exercising at all. So, in a global way the easy way to

call it is the five minute up, five minute down rule. You can do five minutes of

something then you got to take a five minute break. Five minutes then another

five minute break. You add it up by fives not 5, 10, 15, 20. 5,5; 5,5; and keep

adding fives so you recondition, OK.

Supplements. Supplements are aimed at first, good nutrition, but you are very,

very deficient because you use up stuff very quickly so you use up the B

vitamins and your minerals much faster than the next person. So a good multi

vitamin, maybe double the normal dose of the multi vitamin plus a good B

complex. Omega 3 fatty acids because they are anti inflammatory and quiet tumour

necrosis factor but they don’t do it til you get up into the 4g range so one

of those little caps isn’t enough. You need to get up to 4, 5, 6.

CoQ10 was anti-fatiguing but it was just the best antioxidant tested. Just

absolutely sucked up all those free radicals better than anything else. They

used a dose of 60 twice a day but they are tiny little people so do the maths

for yourself. If you are twice the size of a Japanese person you might just want

to double up on that CoQ10.

Inosine. There’s a drug called Isoprinosine, Immunovir, that’s a

pharmaceutical grade neutraceutical. Then we presented at the Reno meeting our

own open label work with a hundred patients. And we had a very nice response,

both immunologic and clinical response in the majority, 85% of the patients that

took Isoprinosine which is Immunovir. Now, Inosine is the over the counter

variation on that theme.

If I can go back to sleep for a moment. Non-restorative sleep is a big problem

for chronic fatigue patients. It’s one of the diagnostic criteria. Anyone here

who’s ever had a restorative night’s sleep with chronic fatigue can tell me

that when they do have a good night’s sleep they do have a better day. What we

presented at the Reno meeting was our own review of charts and found a

surprising number of chronic fatigue patients that develop apnoea over time,

sleep apnoea. You’re so debilitated that you have a disabling fatigue, you

have a justification for a proper sleep study. So I guess the studies.

There’s a drug that’s in clinical trial for fibromyalgia, it’s called

Xyrem. It’s a stage, slow wave sleep inducer and it puts people out very

quickly in just 20 minutes, 10 minutes, sometimes 5 minutes. You take it at the

bedside, you go down to a deep sleep. Now, during deep sleep is when you make

your hormones at night and it’s a really important thing and most of you

don’t have any slow wave sleep. When you get your sleep studies you’ll find

you’ve got none and so inducing slow wave sleep might be good. Xyrem has had a

successful fibromyalgia clinical trial and it is at the FDA trying to get the

fibro label on the drug so that’s probably going to be the one that’s going

to be reimbursable by your health insurance claim.

Reply With Quote

Final section

Question: If you were going to guess on a timetable for, number one, for the

test, when they would have a good test? And, number two, when you would think

they’re going to have a drug that’s going to help the symptoms? If you were

going to guess right now, what do you think the timetable is?

Klimas: Well, number one is easy, I think number one will come very

quickly.

Question: I think six months…

Klimas: Yeah, I think six months is possible.

Question: What about drug therapy/treatment?

Klimas: How fast could you do a Phase I, a Phase II and a Phase III? And,

if we’re considered “orphanâ€, which is the big if, Phase IIs can, in the

“orphan†world, be something called “a II slash III†[a II/III]. You can

start it as a small study and, if it’s looking good, you can just roll it

right on into the Phase III. You can keep on going. And, the FDA typically

requires two Phase III studies for a drug approval - two years, three years? It

could be very quick.

Question: When I fly from north to south, it seems that I really crash

afterwards, I find it really hard to recover from that.

Klimas: You guys are about a litre short in blood volume, ok? If I’m

sitting at five litres, you’re sitting at four. So, you’re really, really

sensitive to blood volume changes. If you’re a little dry, you crash. You’ve

got to hydrate so aggressively when you’re in dry areas.

Question: Unfortunately, I’m not one of your patients. I’ve tried for many

years to get in but…

Klimas: This tells you how terrible this is: I have a 350 patient waiting

list. Ok, and there’s no place else. And, I can’t practice… I mean,

there’s no way to do it all. That’s why, with the help of Hanna, we were

putting together this clinic. A model clinic open in Kendal – we’re going to

have our opening in December. But the point of it is…

Question: Can I ask something else?

Klimas: Yeah, sure.

Question: Some of us may not be able to afford the clinic. That’s a concern

for me.

Klimas: Right, that’s why we’re growing the University of Miami clinic

at the same time. I’ll just say, I wish I could solve this problem for

everybody. But, at the University of Miami we have very generous patients who

donated a salary line for a physician to do nothing but Chronic Fatigue

Syndrome. Which is amazing! It’s taken us a little while but we have the

doctor hired. She’s going to start in January and we will more than quadruple

the volume of our clinic here at the University of Miami which takes all

insurance.

Question: How can we get into research…

Klimas: Oh, you don’t need to be a patient to be in a study. Studies are

for everybody and you don’t pay to be in a study, in fact, often the study

pays for you.

Let me talk about research for a moment. This tele-health study is a really cool

study. It’s the brainchild of years and years of research where we found that

Cognitive Behavioural Therapy can really help people take control of their

lives. The first studies we did were group therapy here and you had to get here

and some of our patients were too sick to get here. And, we didn’t know

whether or not we could generalize and say: Yeah, it’s great for everybody.

So, we designed this other study and, at home, you take the group on the phone,

it’s a tele-health - they give you this phone and fix you up with a group and

there’s a Cognitive Behavioural Therapy group on the phone. It’s very neat.

We also have the “Good Day/Bad Day†study I referred to before. I don’t

know who’s here from my group besides Mack, here. We still have room for, I

think, 70 more patients in that study – lots of room. That’s a neat study

because we’re trying to develop bio-markers and we see people four times and

we do these very expensive and comprehensive evaluations with all kinds of

immune and other kinds of lab tests - they’re all yours, free, they pay you

$20 to come.

We have the Gulf War Illness study that has a Chronic Fatigue Syndrome group.

And, that is a genomic study.

So, the point of our group here at the University of Miami has always been to

advance the science. To advance the science, we have to have study subjects and,

frankly, my original reason why I had a clinic was so that somebody was taking

care of people so that I could recruit my studies. But, then I got sucked in by

you all and I love being your doctor.

[Guest guest]

Sloan

Follow this thread. It is on a transcript of a very poorly transcribed lecture

of Dr K to her chronic Fatigue folks. (The actual CFS people did this work),

amazing how committed they are considering how ill they are. I have attached the

best copy I have and it does a good job of arguing when and why to get tested.

From: Bill klimas <klimas_bill@...>

Subject: The transcript of the lecture posted yesterday

Date: Friday, December 18, 2009, 1:11 PM

Guys

I understand that the lecture posted yesterday was to CSF people and about how

XMRV would effect this group but if this new bug is a key factor in Autism this

same information may well be pertinent to all of us!

The CFS chat group transcribed the lecture using different members for different

sections but I cut and pasted the various parts together. There are typos and

inaccuracies but all in all it is very enlightening!

Klimas

Section 1

Dr. Klimas

“Thank You.

So what brings us here today is this new discovery that you all might have seen

in the paper.

(skips)

Erm, let's. Can you just dim the lights down so that people can see that slide

OK. That's great, super.

So let's just go ahead and get stared.

I'm starting with a little background stuff.

There's three parts to my talk,

OK.

Part 1, a little background for those of you who that are sort of new to the

world and don't realise all the work that's been going on.

Part 2, all about this virus and it's implications. Most of my talk's about

that.

Part 3, is plenty of time for questions and answers, so there's going to be a

lot of informal time. That's usually the best anyway, so if I get too long

winded, you all can just tell me to stop.

(laughs)

I do get excited.

(Image of four faces shown, with text above:

“CFS/ME and Viruses

Chronic Fatigue Syndromeâ€)

Some of you might recognise this. This is the CFS faces project from the CFIDS

Association, the CAA. It's a really neat thing they have that goes around the

country and shows up in shopping malls. But the point of the faces project is

that it's an invisible illness. The people that have this illness look fine, but

they are not fine. And it's a very important message, because

Chronic Fatigue Syndrome's a very debilitating condition.

And there's been research that looked at how severely ill people are with

Chronic Fatigue Syndrome.

And it was the same, or worse than, congestive heart failure.

The same, or worse than, very late stage AIDS.

It's very impressive how very ill people are.

And of course, most of you all are living it, but some of you might not realise

that the science bears that out.

It's been a hard illness to understand, because we had to diagnose it by

symptoms only, OK.

But the symptoms are pretty impressive, and some things are special, to really

help make the diagnosis.

One is the profound nature of the fatigue. It's not that 'Oh I'm tired to

fatigue', it's the profoundly debilitating fatigue that prevents you from being

able to do the normal things that people try do in their lives. And they defined

that by saying, you cannot do at least one aspect of your life well.

If you're

working, that's more or less all you're doing, you're not taking care of your

family.

If you're trying to take care of your family, you probably aren't having any

real social or recreational time, or work for that matter.

So it takes away the very big, and crucial ways that we define ourselves as

people, and how we value our contribution.

But it's also defined by pain and inflammation. Muscle pain, joint pain, sore

throat, tender lymph nodes, headaches, non-restorative sleep and most

importantly, concentration and cognitive problems that can interfere with your

ability to be as quick as you would like to be.

Slide shown during previous section:

Definition - CFS

>6mo. dibilitating fatigue, unexplained by preexisting illness or psychiatric co

morbidity, and at least 4 of eight symptoms criteria:

post exertional relapse

concentration and cognitive complaints

myalgia

arthralgia

sore throat

painful lymph

nodes

new headaches

unrefreshing sleep

There's also a clinical case definition. That was a research case definition.

The clinical case definition was more of a teaching thing, to try to teach

doctors who use this that there is something underneath all of that.

That those are autonomic symptoms.

That those are immune symptoms.

That those are neuro-endocrine symptoms.

Then they cluster those symptoms around the type of underlying system that's

acting badly to cause those symptoms.

This was a clinical case definition made by an international group in Canada,

and I was a member of that group.

I wasn't a member of that first group.

I didn't name this disease. No one blame me.

I was not there. I was not invited.

Slide shown during previous section:

CFS/ME Clinical Case Definition

1 Substantial reduction in activity level due to new onset, persistent fatigue

2 Post exertional malaise

3

Sleep dysfunction

4 Pain - myalgia, headaches

5 Neurologic/Cognitive Manifestations

6 At least one symptom from 2 of the following:

Autonomic manifestations eg. OI, IBS

Neuroendocrine manifestations eg. temperature intolerance, weight change

Immune manifestations eg. tender lymph nodes, sore throat, flu-like symptoms

Link to full report www.iacfs.net

There are overlapping conditions.

About 60% of the people with Chronic Fatigue Syndrome also have Fibromyalgia.

Fibromyalgia is a painful condition, and that's what it is, it's a painful

condition.

It's defined by pain. You poke people in eleven different places, sorry,

eighteen different places

and if a lot of them, or more hurt, then they may meet the case definition.

Slide shown during previous section:

Other overlapping conditions

Fibromyalgia

Gulf War Syndrome (VA CSP 16 fold increased risk of CFS in Gulf War veterans)

Eisen

et al Ann Int (?) Med 2005 7.142(11)??1

Multiple Chemical Sensitivity

(plus image of 'Classic 18 Tender Points')

But underneath that is a very complicated cause.

There's a pain ramp up that happens in the spinal cord and brain, sending more

and more and more pain signals up to the pain centre, and even very light, non

painful touch can be very, very painful.

Even.. you've heard people say, even my skin hurts.

Slide shown during previous section:

Fybromyalgia

Based on the 1990 ACR classification guidelines:

Historical feature = widespread (axial) pain of 3 months or more

Physical finding = pain in at least 3 of the 4 body segments + a finding of at

least 11 tender points on digital palpation of 18 designated tender points

No exclusion criteria

(??? et al, 1994; Portenoy et al, 1996; Wall et al, 1994; Wolk (?) M, 2002)

(plus image of 'Classic 18 Tender

Points')

Gulf War Illness is something near and dear to my heart, and I know Mac (?

Matt?) cause we both do research in this area.

We have some Gulf War guys in the audience here.

Gulf War Illness can also meet the case definition for Chronic Fatigue Syndrome.

They overlap, and much of our research in Miami is trying to decide if they are

the same or not.

And if they are, you know, if the treatments might be the same.

That's one of the main focuses we have, and we have some really cool studies

going on.

And I want the Gulf War guys to know, that I shipped off those boxes to the

Whittemore Institute yesterday, so anyone who's in my Gulf War study,

is having their XMRV serology and blood testing done very shortly. So I'll be

getting back to you as soon as they tell me. So we'll know if it's truly

overlapping in the same ways.

And then Multiple Chemical Sensitivity is an even more poorly understood,

difficult

illness, to have, and a difficult illness to diagnose

One of the issues with Chronic Fatigue Syndrome all along has been the attitude

of physicians. And there have been a number of studies done (Lenny (?) did

one, this is a different one), that looked at the attitudes of doctors who don't

even recognise the illness is real. And it works out about 50/50. And the

doctors that do, generally have a family member who's ill.

Generally speaking their connection's not their speciality or their training or

anything else, it's that they're linked personally to a person with the illness.

Slide shown during previous section:

Attitudes of Physicians

Of 811 GP's 44% did not feel confident making the diagnosis, 41% did not feel

confident treating

More likely to have confidence if they had a friend or family member with CFS,

having more patients with CFS.

Concludes that education emphasising acceptance of CFS as a real

entity results in improved confidence in treatment

(Couldn't read source, ended (April 1))

So, what about viruses?

We found most of the work that's been done on Chronic Fatigue Syndrome has been

on mental illness, and depression, and atypical depression. And the patients

have gotten a bad rap.

And I'm gonna say this in sort of in a funny way.

This is my own personal opinion, that part of the reason that there's so much

psychology work done is that this is a very interesting illness from the

psychologist's point of view. As is any really serious chronic illness.

Patients with HIV have a huge mental health literature.

Patients with renal disease, or renal failure, have a huge mental health

literature.

Because one thing you can really do for people with a chronic disease, is try to

help them live with it, cope with it better, and try to have the best quality of

life that is reasonable.

And so, most of that mental

health literature is actually focused on that.

All that Cognitive Behavioural Therapy work and so on is focused on that.

I think where Chronic Fatigue patients got really angry, and I totally

understand, is when some researchers went off on the tangent that this is some

atypical form of some primary mental condition.

And I think we disproved that in 1993 or 4. I mean it was a long, long time ago

that all those endocrine studies came out that showed that basically the illness

goes in the opposite direction from all the neuro-endocrine point of view, than

depression or that sort of thing.

But still, there's been this cloud lying over folks with this illness because we

never came up with a very clear understanding of what the primary cause might

be.

And much of the excitement about this virus, is that it is itself a candidate

for being a primary cause.

So it's a very exciting time.

Slide shown during previous

section:

Viruses and CFS/ME

Much of the research here and internationally has examined the role of the

immune system and possible chronic infection in CFS

The viruses studied all have several things in common:

they infect cell of the immune system and the neurologic system;

they are capable of causing latent infects;

they can reactivate under certain conditions

Section 2: Viruses & CFS/ME; WPI & XMRV

The other half of the medical literature was looking at pathophysiology, just

what's wrong. And this group in Miami has from the very first day, actually the

very first group, to look at the immune system as a major mediator of the cause

of this illness. In 1989 we wrote a paper from our first series of patients that

show that the chronic fatigue patients had immune activation and poor antiviral

cell function. We wrote that paper in the Journal of Clinical Microbiology back

at the beginning, very early on,

and a couple papers right after by Jay Leevy's group that say the same thing,

and that’s what launched us in this field.

So we've been focused on viruses from the very first day. So what do we know.

The very first day we looked at Epstein-Barr virus and other herpes family

viruses. Epstein-Barr and Cytomegalovirus were the first viruses that were

looked at. Dr. Leevy's paper and my own and others said, what we saw in all

these virus serologies we looked at, when we looked at the antibodies, was EBV

is there, we can't say it's not. There's all kinds of other serology for other

things that didn't pan out. But Epstein-Barr over the years, time after time,

there's been at least a subgroup of patients that looked to have a higher level

of Epstein-Barr virus than they should have. CMV a little less so.

In the 1990s two things happened. First, Elaine DeFreitas and Mike Holmes from

New Zealand both published papers at about the same time,

1991-92, saying that they saw a retrovirus in chronic fatigue syndrome. And Dr.

Holmes paper had all these beautiful scanning electron micrographs of little

budding viruses coming off of white blood cells that looked for all the world

like a retrovirus. And Elaine DeFreitas who was at the Wistar Institute at the

time published a paper that said she had fairly good evidence that there was a

retrovirus.

What happened next was a little complicated, partly from our point of view--we

recruited Elaine down at the University of Miami and she joined our faculty, but

unfortunately she became very ill very shortly after and left. So we never got

to pursue her work which is a shame. I’m sure she’s feeling very good right

now about this new work. The other thing that happened was that the Centers for

Disease Control published a paper and presented at a number of conferences that

they failed to find that retrovirus. And it was a shame because that was how

it was left. There was this positive finding from two different groups, one

group saying absolutely not, and then nothing much went further from there. So

we lost unfortunately that time from then to now. I’ll have to say though, we

didn’t know this virus hadn’t been identified yet. I don’t think it would

have been a rapid thing there, but certainly we would have been further along

than we were now.

The HHV-6 was the second big thing that happened in the middle of the 90s. This

other new virus was discovered, human herpes virus type 6, the virus that also

causes the three day measles, another childhood virus—another herpes family

virus. And it turned out to be reactivated in a whole lot more people than the

Epstein-Barr virus. So this was the first virus that got a lot of credibility as

really being there by all the groups that were looking. And there was some

excellent work, Dharam Ablashi who was the discoverer of the virus,

discovered the virus, Connie Knox, and a private foundation, the HHV-6

foundation, that did some excellent fundraising and really did some pointed

research to drive this home and push that along to the point where clinical

trials had been going on to try to suppress this virus, with some efficacy. So

that was very exciting.

So then we enter this decade and we’ve got enteroviruses. That’s Dr.

Chia’s work, where he did a lot of gastric biopsies and he found coxsackie

virus, which is a whole different family of viruses also very common

reactivated, and he found it in the gut wall with a gastroenterologist who was

biopsying stomach. And they found virus.

So it made us stop and think, well wait a minute, if the immune system is broken

enough that more than one kind of virus is getting out, how are we going to

focus our work so that we’re covering this immune system problem. Instead of

trying to pick off one virus at a time should we

maybe be backing up and saying can we fix the immune system that’s broken and

prevent these common viruses from reactivating.

And then finally we come to this definite landmark paper of October 8th in

Science by the Whittemore ’s group with Judy Mikovits and Vince

Lombardi. It is a very important paper, and the reason why this paper is so

important is that this virus is a really good explanation for why the immune

system is broken, unlike the others. This one would explain why the immune

system is broken. And it is also a really important paper because this virus is

not common. There are very few people that have this virus, and yet most chronic

fatigue patients in their study did have this virus, and so it’s a candidate

virus for causation. And that’s, I think, why everyone’s so darn excited.

I put up this slide because this is going to be videod and someone is going to

read this who’s not here, and I want people to

know when I’m using someone else’s slides. I borrowed these slides from Dan

and the Whittemore foundation. These are the people that work

him on this, and even though I wasn’t part of this particular group, I feel

like I’m a member of their family because I spent a lot of time in Reno when

they were first setting up, and I really admire these people. They’re really

very talented. So there at the Whittemore Insitute...even though

Annette Whittemore’s name is not on this slide, it should be right up there on

the top. Annette Whittemore is the reason why the Whittemore Insitute

came to be. Harvey and Annette are these lovely people who know how to get

something done. Their daughter is very ill, and they realized that they were

getting the best possible care because Dan was their doctor. And they

said how sad it is for people who don’t have access to such talented doctors.

So they established this,

the WPI, Whittemore Institute.

And then in a very targeted way and a very brilliant way, they said this is the

kind of research we want to do what we want to focus on, and they made a team

that could do that. They were absolutely virus hunters, they were looking for

viruses, and they put a team together to find viruses. And they got an excellent

team put together, and by gosh, two years into this work and they have scooped

us off. Good job. So they did a fine job. And they did that with their

colleagues at the NCI, Ruscetti, who’s a very famous virus hunter in

oncology, is one of their senior partners and that whole team there, and then

Bob Silverman at the Cleveland Clinic with Dr. Gupta. These are two people, Dr.

Silverman’s one of the discoverers of XMRV several years ago and he was a

member of the team that went after it. So it’s very impressive work.

---

XMRV Virus Section 3

So what is this virus

X-M-R-V? Well, the RV means retrovirus. So that puts it in a family of viruses,

retroviruses, that we actually know quite a bit about. And the X is xenotropic.

M was mouse. This virus started in a mouse. Now there’s…ya know viruses

start somewhere. They’ve got to start somewhere. Like the HIV virus started in

a monkey. It’s a monkey virus that eventually evolved several hundred years

ago into a virus that could infect humans. So we got this lousy virus, HIV.

XMRV is in its own evolution. And it jumped from mouse to human at some point.

We don’t know when, but probably not in the too terribly distant past. Well,

that doesn’t mean a lot, because in Darwin terms, distant past could be 100

million years, but these guys think like that, the evolutionary biologists. That

wasn’t long ago, a thousand years ago or so. But in this mouse virus, it could

have been in the last century. That’s the sense of it.

About 3-4% of people have

this virus and they’re not sick. And that’s another part of this. So

there’s this background population. Now, I’m just saying that flat out, but

you know I gotta tell you that the research on this virus is only 2 years old.

And so, we don’t know very much about it. And there’s probably regional

differences. There might even be continental differences. We don’t know.

There’s been nothing done anywhere else. They did some studies – originally

this virus was found in prostate cancer. So most of the work was done in that

area and there’s two studies: one in Germany and one in Ireland that failed to

find this virus in their patients. Now, whether they’re using the same

technique or it’s not in Germany, it’s not in Ireland, we don’t know. So,

there’s a lot of questions still to be answered with this virus.

This Science paper was amazing for a number of reasons. First, this team had put

together such strong science that

they could go for a Science paper. And for those of you who aren’t in the

land of science, Science is like the Mecca of publication. If you get your stuff

in Science, that’s the best place you could possibly put them. And they

don’t take just anything and they sure, sure, sure don’t take something

unless it’s extremely well done, validated and tested out. So they took this

paper. And if you read this paper, they not only took it, they put it in Science

Express. They thought it was so important, they published it on a very fast

track. And so, that was important.

And if you read the paper, you’ll see that found this virus the first way they

looked. They backed up and looked from a whole different angle. Still found it.

Backed up and looked from another angle. Still found it. Then, in two other

ways, they had five different kinds of ways they looked for this virus. And they

were able to find the virus. So I think that’s why Science was

so impressed. They also used a very big population. They had 100 Chronic

Fatigue patients – 101. And they had more than 200 controls. So that’s

usually…scientists like that kind of stuff.

And then, the interesting thing was in this paper, the first 20 patients they

studied were Chronic Fatigue patients that had developed some kind of Cancer.

That’s actually how they got the Cancer guys’ attention, I’m assuming.

Because Dr. ’s got 30 years of stuff in his freezer and dug out

everybody in his whole population that had ever gone on to develop Leukemia or

Lymphoma or any other kind of Cancer. They pulled those out first and that’s

actually where they first found it and that’s what got their interest up. And

then they went back and looked at a bunch of others. The way they looked is very

sophisticated and they found 67% that way. And then they tried to find it in all

these other ways, when they added everything together, they

could find the virus in roughly 95% of the patients using one technique or

another, but not necessarily consistently, no matter what technique they used.

But it means that there’s at least 67% of people in that Reno cohort and

possibly quite a bit more.

So what is this virus? It’s a mouse virus. It was first discovered in 2005. It

was discovered by prostate cancer researchers looking for a virus, viral causes

of Cancer. So they found it in that study in 40% of prostate cancer. Another

group looked and found it in 23%. And so there have been two studies that said:

the virus is in prostate cancer. Other groups though, have not found it - in

Germany or Ireland – so it’s still considered somewhat controversial. It’s

a different strain than the one seen in prostate cancer. It’s not exactly the

same. Okay? I’ve already had patients whose husbands had prostate cancer

thinking that they somehow infected their husband. Oh my God, I gave my

husband prostate cancer. Don’t think that way, okay? It’s a different

strain of the virus. They’re related, they’re closely related. But we

don’t know enough to even pretend to go that far with assumptions.

It’s a virus that doesn’t have a lot of mutations. And what that means to

the virology world is that it doesn’t change very much, it’s not shifting

around, there’s not a whole bunch of different kinds of it. Like there is with

HIV, where within a few weeks of applying an antiviral, the HIV virus can mutate

away and escape and go off and do its own thing. So this is a pretty stable

virus. That bodes well, particularly for vaccine work. That bodes extremely

well. We don’t know what that means to the antivirals yet. It just depends on

how much replication is going on.

Why does it fit into Chronic Fatigue? Well, there’s a lot of good reasons why

it fits in to Chronic Fatigue. Those of you who live and breathe this

stuff might have heard me talk about natural killer cells a little bit.

((laughs)) NKs are really broken in Chronic Fatigue Syndrome and natural killer

cells are part of your defense that prevents latent viruses from reactivating.

And they really, really don’t work well in Chronic Fatigue Syndrome. And our

group has done 20 years of work to try and figure out why – and we know why.

And we also extend that to say: these natural killer cells that don’t work are

closely related to a different cell, cytotoxic T-cells. And they don’t work

either and between the two of them, that is your antiviral, latent viral

reactivation system. Both of the systems are broken.

So, enter a virus that infects and affects natural killer cell function and

that’s this one. And infects and affects T-cells, cytotoxic T-cells. That’s

this one. So we’re kind of keen, we don’t know for sure, I mean this so

early in the work, we’ve gone all of three weeks

since that paper came out. There’s going to be a lot of work to be done. But

it would make a lot of sense, a good hypothesis to construct if this virus is in

there mucking up cell function, and that would make a lot of sense to what’s

going on.

It also is a virus that can infect tissues that aren’t white blood cells. And

we’ve always thought: something like that has to go on in Chronic Fatigue

Syndrome because you all have some neuro-inflammation. Your brain has a low

grade level of inflammation. And you have some inflammation in the tissues that

make hormones, particularly the hypothalamic-pituitary axis. And this is a virus

that has some tropism or infects that type of tissue. So it starts to make the

whole picture come together. Now we don’t know enough about this virus’s

tropism or what stuff it likes to infect. This is just sort of the first look

and some of this may change as we get more sophisticated and look with better

ways.

But the sense is this virus, if it’s acting like its cousin virus HIV that

likes to infect those kinds of tissues, that it’s going to have receptors that

let it into other places too. Anyway, I think it fits well and I’m very

excited about that fit.

And 4

When we talk about latent viruses, this is what we’re talking about. The guy

on the top is a quiet little white blood cell hanging out doing nothing because

no one has asked him, it doesn’t have a job yet. If it becomes activated,

it’s because something floated into the system, some antigen, some bug that

it’s supposed to respond to. And in our systems we have hundreds of millions

of these little quiet cells and each individual cell only knows its one little

job.

Now this one’s for Epstein Barr, that one’s for Staph, and that one is for

some other bug. If that bug comes into the system, then that cell is the one

that gets activated. And if it had hidden

inside it, in its DNA like over there, if it has inside it this little piece of

virus fragment, sitting in that DNA, that cell is turned on to make all of its

stuff it knows how to make. It got activated. It’s going to make cytokines,

it’s going to make interleukin 2, it’s going to make ?? , oh and by the way,

it’s going to make that sneaky little virus that was tucked into its DNA too.

And that’s what happens.

These latent infections just sit around doing nothing until that cell is

activated and then boom, they start making virus stuff. Retroviruses are funny

because we’re just chock full of them. We have little bits and pieces of

retrovirus all in our DNA. Talk about evolution, our great, great, great, great,

great, great, great grandfathers got infected with some little piece of

something, maybe a chunk from a mouse back then. But it’s not a whole virus.

They have just little bits and pieces, of bust up pieces of retrovirus

tucked in the DNA. We think it’s an important part of the way that we

evolved. That we borrow DNA from other species this way and we transfer things

around. If viruses carried little pieces of information into the genome back

then. And some of it was bad and that didn’t work out. And some of it was good

and it carried on or it was neutral and it carried on.

But there are some retroviruses that can be carried generation to generation as

a whole and complete virus tucked into that DNA or rather enough DNA to make a

whole and complete virus when it’s turned on. And this is one of those

retroviruses. It can be transferred generation to generation or what’s called

vertical transmission, mother or father to child through the DNA. So we don’t

know if there’s 3 or 4% of background. There’s just people who have vertical

transmission or if there’s some way that you can infect people back and forth

in life. We don’t know that at all,

okay?

But we do know that this virus is one of the ones that is vertically

transmitted. We know that from the mouse data. So it can be transmitted

vertically. So the question is if you have children, do your children

necessarily have it? And the answer is maybe yes or maybe not. First off,

there’s two parents not one. And each only give half of the DNA, yeah, right?

So in any given child, there’s only one chance in four that you can pass on

any particular piece of DNA on a good day. So you don’t worry too much about

kids flat out that way. And then you say: And oh, by the way in their life, they

have to come across the thing that activates the virus and turns this whole mess

on. And so there’s a whole lot of reasons not to get all worried about…I

mean I’m not saying it couldn’t happen to your children…Of course it’s

conceivable. But what’s exciting right now is we’re getting this, we’re

getting the understanding of it, and

we’ll probably, knock on wood, that we will be to the position where we’re

actually intervening effectively before it becomes a bigger worry. But, um, I

don’t know about kids. I’m saying it is a vertically transmitted virus.

We don’t know if it’s sexually transmitted. I will say that there are

sexually transmitted retroviruses. We know HIV is, obviously, is a sexually

transmitted retrovirus. But, there’s no…you’d think in 25 years, we would

have seen massive numbers of spousal pairs. And we have not. You occasionally

do, occasionally we do see a spousal pair. It happens. But almost always those

people both had acute infection at the same time at the onset and it’s really

unclear if it was transmission between the two of them or if they had some other

thing happen that kicked off the whole, the whole thing. And you see household

Chronic Fatigue. I mean I do see mother-daughter, father-daughter, father-son,

whatever…I’ve

seen it. But, in my clinical practice in the 25 years or so, it’s not very

common. It doesn’t happen a lot.

So, the next slide. This virus is not HIV. A lot of people panicked when they

heard this. This virus really is not HIV. It’s in the same family, but it’s

a distant, distant cousin…very very distant. And it’s not infecting or

affecting the same cells. So, it’s not doing the same immunologic thing that

HIV does. Okay?

There are also other retroviruses that don’t do anything that we know about.

There’s a virus called HTLV-2 that I have studied myself in the past, and many

others have, and it’s just sitting around doing nothing. It’s

really…it’s vertically transmitted, it even replicates, and it doesn’t

cause much in the way of illness. So, that doesn’t necessarily mean that just

because you find a retrovirus, it’s definitely the deal. And not every

retrovirus is big and bad and ugly. There’s another

virus called HTLV-1 that’s vertically transmitted and does cause an illness.

And it causes a neurologic illness. And so, we have different bugs, different

things.

HIV is a retrovirus and there’s at least 20 or more drugs directed at HIV. So,

will those drugs work to control this virus? That is definitely the big question

of the day. And the first thing to say is: some of them probably will. And the

second thing to say is, but not all of them…you couldn’t just pick a random

one and try it.

This one’s to show you mouse going to people…that basically it started out

way up there as a mouse thing. Mice learned to live with it. They don’t have a

receptor that allows this virus to become a big bad deal. So, mice just sit

around for generations and generations of mice being a reservoir of virus, but

not actually getting sick from the virus. But then the virus shifted and it

became capable of jumping from species to human.

So,

this was the study. They had in their freezers samples from people that

weren’t from their cohort. So, these were not just Reno samples. There were

samples from Florida, from California, from North Carolina, and other places.

Everyone in their repository had a Chronic Fatigue diagnosis. The mean age was

55. There was two thirds women. They had this large control sample. They

looked…and they looked at these patients, out of 101 patients, and they looked

at the DNA, the sequences of the virus in the DNA. It’s really a sophisticated

way to look and they found it in 67% and in 3.75% of the 320 controls.

Now of the negative, these 33 negatives, they went on and looked in other ways.

And they found 19 of those had antibody in their plasma, so that was more than

half of those negatives. But this is the big number: 30 of the negatives had

virus they could identify by taking the serum of those cells, the serum from the

plasma, and infecting a cell

line and then growing the virus in that cell line. So they could transfer from

the plasma, virus to the cell line. Now that has a lot of implications and

it’s certainly the reason why, in part, the CDC, the NIH, and others that

really care about the blood industry are looking long and hard at this. They

found the virus, a transmissible virus, in the plasma and they were able to

infect cell lines. So it is suggestive of an infective component, at least in

the blood. And then there were other ways, so they worked out that they were

able to find 99 of the 101 patients in that way.

Now think about that for a minute. We define an illness by a bunch of symptoms.

Now, I’ll say Dr. is a really fine doctor, and I’m quite certain

that he’s not misdiagnosing Chronic Fatigue Syndrome. He’s really splendid.

So, it could be that he has a really clean, tight population of folks in his

freezer. But I would say, I think I’m pretty damn good,

and I think if I pulled out stuff from my freezer, there might be a couple of

MSs in there or something else that evolved down the line. I mean, I’m not

sure. But it’s pretty impressive that out of 101 CFS defined by clinical case

definition or a research case definition that they found 99 with virus. And if

this is the case, that’s pretty exciting. It’s pretty impressive. And, oh,

by the way, we have a biomarker. Not a small deal. A biomarker – the virus

itself. No better biomarker than something that’s clearly, tightly associated

with an illness.

Section 5 – Antibodies, What we don’t know, Cancer

Antibodies

[Question from audience, inaudible]

Oh that’s a really good question. She asked: " If there’s antibodies why

don’t the antibodies kill it? " That’s a very good question and one that dogs

the vaccine-development people in HIV all these years. The reason we don’t

have an HIV vaccine yet is that

antibodies don’t kill HIV, you need cytotoxic T-cells to kill HIV. So all

those vaccines for HIV have been trying to get the cytotoxic T-cell lines all

geared up and ready to go and not focus on the antibodies. The antibodies

don’t do it. Whereas for other viruses the antibodies are great for it. I mean

all those childhood vaccines you got were just trying to build antibodies for

all those years. So there are some viruses that just the human body doesn’t

make a killing, lethal antibody to attach to that virus. So we don’t know this

virus well enough. I don’t know, there might be an antibody that kills this

virus. It’s only been a few years. They haven’t had a chance to look very

hard. The other thing disturbing on that other one was only half the people they

looked at had antibodies, but they had the virus. So antibodies are probably not

going to be our world’s best blood-test for this.

Judy Mikovits renamed the illness, I’m not

sure this is going to stick, but she called it XAND. XMRV Associated

Neuroimmune Diseases. The reason why I don’t think it’s going to stick is I

don’t think the “M†is going to stick very long. I think as soon as this

virus is clearly shown to be a human virus, they are not going to call it a

mouse virus any more, and they’re going to rename this virus, and then we’ll

be renaming again. So I’m not leaping to embrace the new name, but I will

embrace any name that’s not Chronic Fatigue Syndrome! [Applause]

Slide: XMRV Associated Neuroimmune Diseases (XAND)

Potential Candidates:

• Atypical MS: 3/3 positive for XMRV ENV protein and gag DNA

• Fibromyalgia: 12/20 (60%) positive for XMRV gag DNA

• Autism: 6/15 (40%) positive for XMRV gag DNA

4/7 (57%) positive for serum antibody to XMRV Env

• Gulf War Illness: Not tested

Samples were taken from family members of XMRV positive

CFS

subjects with these neuroimmune diseases.

This is also stuff they showed just last week, and this is not published data.

And these are not going to be very representative because these are family

members of CFS patients, who happen to have MS, fibromyalgia, autism. And in

family members of CFS patients who had these other conditions they found XMRV in

that family member. So there are lots of questions. This is the first paper. The

paper is very exciting. The next step is to validate the paper. The very next

step. And this is going to be difficult because what did I tell you about the

prostate work? Two of them said yes, and two of them said no. Now if you talk to

the guys who said yes, they’ll say the guys that said no didn’t use the same

method to look. That’s science! We do this all the time. We get into big

quibbles over method. Method, method, method!

Already I have a conference call with the CDC on Monday because they

want their samples. The guy at NYU wants their samples. The guy at Hopkins

wants their samples. I mean everybody knows that I have a freezer full of

samples and my reaction is: Oh my God, what method would you apply? I don’t

want to be the one that had the bad method. I don’t want my name on the paper

that didn’t use the right tool! So, the first step I think is to get all the

people trying to do this together and use the same method. And that’s

absolutely necessary. And if you see some negative papers coming out, don’t be

discouraged. It’s going to happen. There are going to be some negative papers.

People really jump to do this. And the method is not that easy, and getting the

right bits and pieces you need together, it’s not: read the paper and then go

do it.

Things we don’t know.

What cell types are infected? We know for sure that NK-cells are and other white

blood cells are. We know that there is some neurotropism

[affinity for nervous tissue] from this virus from the mouse studies. But we

don’t know every kind of cell type that could be infected and what’s

infected in humans.

How is it transmitted? A critical question. Certainly the blood bank industry

has jumped right in and are going to try to see if this is a worry there because

they have freezers full of samples they can go back and survey for any positive,

and then actually have recipients, and they can see if there are any recipients

that are positive. So they’ll be able to test that theory I think very quickly

and very efficiently.

What is the immune response that controls this virus? You asked that question:

would antibodies do it? And the answer is (that's a great question) the

antibodies might do it. Cells might do it. It might be that we have to repair

these cells and then they can do it. But those are good questions. We don’t

know with this virus what the answer is. But we do

have a much better sense of what retroviruses are after the last 20 years of

HIV work. We really do. I mean I go to the HIV meetings and I go to the CFS

meetings. Let me tell you the difference. Reno, and this is a pretty big meeting

last year, I think they had 100 and maybe 200 investigators, and that was the

whole world, the Japanese were there, the Europeans were there and pretty much

it’s a who’s who of who does this work and there was 200 of us. And the HIV

meetings, I’ve been to meetings where 18,000 people came [gasps from

audience]. And that’s the kind of brain power that was being directed.

Now the other thing about the HIV guys is that they are kind of bored, don’t

have anything to do, patients are doing well, [laughter] science is a little

dry, not a lot of grants. Cool! We’re going to suck some of those guys right

into our field now. This is going to be really, really good. We’ve been

waiting for a flush of brilliant new

people, and I think we are going to see a flush of brilliant new people come

into our field if this holds up, there’s going to be a lot of good interest.

Cancer

Does this virus alter the risk for cancer? Now it’s a question that has been

left unanswered to you and every single one of my patients has asked me this

question. Do I have an increased risk of cancer? My gut reaction is yes

probably, because the cells that are your cancer-prevention cells are part of

what’s broken or partially broken in this illness. So you always hear me

talking about anything you can do, [e.g.] antioxidants, to try to help you any

way you can to boost up your own tumor-defense systems. And these cells in

particular. But here we are 25 years into this illness and we do not to date

have a natural history study that is longer than 3 years. No one has yet

answered for you the question that needs to be answered. Part of my motivation

to put together these

clinics with Hannah, these Chronic Fatigue clinics, is that we were going to

use this big common database and if we really can get a bunch of clinics all

linked up together using the same database we’re going to have a natural

history study finally. Because you have to do it yourself. That’s how it works

in this field. We actually don’t have that information for you.

Can we develop Immune-based therapies? I and [Dr] Mikovits have been working on

immune-based therapies for years. We did a really cool one years ago with cell

extension. Some of you were in that study and some of you got really big

impressive results when we enhanced your cytotoxic T-cells and your natural

killer cells. You got good clinical improvement.

And 6

And here’s the real compelling question: will antivirals work? This is a virus

that’s sort of coming in to a white blood cell and it’s hunting for its

receptor. And then it’s going to attach to this

cell. This is a retrovirus attaching to the cell. Now in this virus, we don’t

know what that receptor is yet in human. We actually sort of have an idea from

the mouse work, but we don’t know for sure. But there’s an attachment step.

And then the virus enters the cell. It fuses to the cell. In HIV there’s these

entry inhibitors and fusion inhibitors that prevent that so there are potential

therapies if it were the same receptor. I kind of doubt it. I don’t think

we’ll be using those particular HIV drugs.

Then it gets into the cell and when it gets into the cell, it dumps its RNA into

the cell. It pokes a little hole and the virus comes in. And then that RNA comes

out. And we’re DNA, not RNA. The nucleus of our cells is DNA, so it has to be

turned into DNA. And to do that, it uses an enzyme called reverse transcriptase

and that turns the (see I knew before that thing before it told me. I am smart).

Anyway, it turns RNA into DNA and

that is a wonderful target for this virus…the reverse transcriptase

inhibitors…because then the DNA can integrate into the cell. Now we have

integrase integration inhibitors also…in HIV…integrase inhibitors. But they

are fairly selective for HIV. I don’t know that they would be effective in

another retrovirus.

And then, when the cell is activated and its DNA starts making stuff like this,

it has to be…it makes these great big long proteins and those proteins have to

be cleaved into little pieces (see I’m sinking here). And that’s the

protease inhibitor line in HIV, the proteases that cleave are inhibited and that

prevents that piece from being torn up. And then all these bits and pieces

assemble themselves over on the cell wall and they bud off – BOP – and

there’s a virus. And that’s how viruses are made.

So, we have entry inhibitors, we have reverse transcriptase inhibitors, we have

integrase inhibitors, we have

protease inhibitors. And then all those put together is the whole repertoire of

drugs that have been developed over the last 20 years or so for HIV.

But, be it known that there are literally thousands of compounds in the

pharmaceutical companies’ shelves that they developed for HIV that weren’t

as good as things for HIV that approved that might be the very perfect thing for

this virus. So, we’re not starting from scratch here with this virus – at

all! The other thing about this virus, and this is just from what Dr. Coffin

said at the Chronic Fatigue meeting on Friday (I’m not a retrovirologist as

brilliant as these guys) but I can parrot them pretty well. Dr. Coffin said –

because this virus doesn’t seem to mutate very much, it’s a great target for

vaccine trials.

And when you ask - what about antibodies? – if we vaccinated people to this

virus that already had the virus, we could goose up their immune response to

this

particular virus. That’s what they’re doing in HIV trials, they vaccinate

infected people. So you might suppress the virus with an antiviral and then

goose up the immune system with vaccines, so it could really work hard on this

virus and then reduce it. So you could start postulating. Isn’t it fun to be

able to postulate therapies…I mean, it’s great. I’m loving this. I’m

lying awake at night thinking of all these things. It’s like – oooh,we could

do this – oooh, we could do that. Good stuff. I know, I know, I’m an

immunologist, what can I say?

Of course one of the things I think about is immunomodulators – drugs that

would either quiet immune activation or enhance cell function are very

appropriate. Okay, so what’s already out there? Well, Ampligen, Ampligen’s

an interesting drug. And they actually showed – they had 8 patients that had

Ampligen data – that they showed at the CFSAC meeting that Dan showed. And it

had a mixed result. In some cases, Ampligen was very effective in suppressing

this virus, and in some cases it was not – in those 8 patients. That’s not

very many. But Ampligen sounds kind of promising because it’s an antiviral

that’s an immunomodulator that enhances natural killer cells and cytotoxic

T-cell function. It’s even more intriguing than before in my mind, I think

Ampligen’s got some real potential.

Immunovir (Isoprinosine) – some of my patients are on this medication. It’s

only had phase 2 trials, it hasn’t had phase 3 trials. But it’s more or less

a nutraceutical, it’s an amino acid. But it is also an NK cell enhancer and a

cytotoxic T-cell enhancer that may have some antiviral effect.

This cell therapy – I referred to this ex-vivo cell therapy – some of you

were in this study – It was in 1993 or…it was 1993. Well we took a lymph

node from a patient and we grew the cells in a laboratory and we made

literally a transfusion of white blood cells. Max did that. He was busy, busy

transfusing my patients with white blood cells – their own white blood cells.

But in the test, in the laboratory, we had grown them, fixed sort of what was

broken about them, and then we got some very very nice clinical responses in

that Phase 1, that study that never got to go to a Phase 2 study for lack of

funding. And then finally, this makes cytokines that are either directly

antiviral or immune enhancing more interesting.

The nutraceuticals, they have less work done. Omega-3s are anti-inflammatory,

the mushroom extracts that the Japanese use to enhance natural killer cell

function, but these aren’t studies that had placebo control data and looked

promising. CoQ10 at roughly 100 twice a day – that was really anti-fatiguing

and enhanced cell functions. TNF inhibitors, we have a couple few patients on

TNF inhibitors and I’m seeing some nice responses if

they’re cytokines are way wacked out and they’re super revved up.

That’s a natural killer cell, the little guy killing that target cell.

That’s an Epstein Barr virus infected target. And there’s that little white

blood cell doing its job. That’s what we’re trying to do. So the white blood

cells infected with virus and you want these cells to go in there and kill that

cell. So, the other question with this is: okay you’ve got one virus, but what

if you’ve got this virus plus a couple of other viruses? What’s the role of

all these viruses all together? What about HHV-6, EBV, enteroviruses, and this

virus. If we say that all these viruses are doing their work together, it might

be necessary to treat more than one virus. It might be necessary to design a

study that has the retrovirus piece and a Herpes virus piece because sometimes

viruses lend each other machinery to make their infections more potent and

damaging.

Section

7: What’s Next in Research?

(Slide – What happens next?)

What happens next is very clear, research.

Dirty word but the most important word in the whole game. Gotta know that

research has to happen and it is the research that gives us effective therapy.

I started HIV in 1983, is when I finished my residency. And so I started right

here at the University of Miami and I started right in the HIV program before we

knew the name of that bug. And in 1984, the bug was named, and in 1988 the first

anti-viral was tried, it was a little bit helpful but it wasn’t all that

effective. In 1994 we had three drug combinations that just kicked butt. In the

time between 1983 and 1994 I lost 1000 patients. It was devastating, I was

emotionally a wreck every time I went to clinic. And now I am going over to my

HIV clinic at the VA and I am taking care of blood pressure, I am taking care of

hypertension and cholesterol and the usual

stuff. And you know, HIV sometimes does it’s dirty deed which is to say to

make people a little more prone to cancer, sometimes we get some cancers, but

most of my HIV guys are really healthy.

I got into a little trouble in the New York Times for saying this, did anyone

see me in that Times? I said my HIV guys are hale and hardy and my Chronic

Fatigue patients are not, they are not. And that’s true, but I am very

privileged to have been a doctor caring for all those people and then being

there when the time happened when these things changed. You know, there I was an

HIV doctor, dying patients, going to funerals, and taking my patients, doing

rounds of hospice on my way to rounds on the regular wards and then I was there

and in a matter of a few months I had patients that went from 80 pounds to 180

pounds.

And I got guys that I take care of now and I remember them from when they were

80 pounds. I have one guy that played basketball six

hours a day, he’s the most muscle bound handsome guy you ever saw and he was

nothing but bones and that’s because I stuck it out and I feel really

privileged that I got to be their doctor and see them all the way through but

that’s how I feel about Chronic Fatigue Syndrome right now. I mean, I’ve

paid my dues. You guys have certainly paid worse dues than I’ve had to pay on

this. But I’ve paid my dues, I’ve had the privilege of being your doctor and

watching you bear through all of this. And I really think we’re at this point

now where I am going to get to be there during this wonderful transition from

really sick to hale and hearty and that’s what I am really looking forward to.

So we’re going to do that, right? (applause!).

So what’s next with research?

(Slide - What Happens next?)

And the research is going to be a lot of different kinds of research. We’re

going to have to do basic science research to

understand this virus. The first step is just to validate that study that was

October 8th in Science which is already going on, but there are probably ten

other studies going on. Now I am going to do that too. To see how far it

extends. Is it in Gulf War Illness? Is it in Fibromyalgia? Is it in autism?

That’s a really interesting question. I mean for my nephew’s sake, I really

hope it’s true. And so on. There are some real possibilities here. This virus

has been a sneaky virus messing people up in more than one way for a while, or

it might just be a Chronic Fatigue/ME virus.

The next step is in culture - what drugs work? What drugs that we already have

that we can quickly roll out in clinical trials work? Meanwhile, in the back,

what other drugs are on the shelf that might be even better than the one that

are already out there for HIV? And we’ll be able to do those phase one and

phase two trials very quickly. They could happen very, very

quickly. There’s a lot of motivation here. You guys are sick but there’s

also one million of you, you’re a hell of a market. And that’s just the

United States.

So if we have a biomarker that we can diagnose with, which is a huge step

forward and we have a treatment, a potential treatment, then I think you’ll

have the attention of Burroughs-Wellcome, and Roch and Abbott and all the

companies that have anti-retrovirals as their primary deal. The

immuno-modulators, don’t leave us immunologists out of the big push forward. I

think immuno-modulators may well have a role.

Sub-grouping patients by different things, could be, here’s a big make

believe, but what if it is autism? What if you get a virus in your head when

you’re 18 months old? What if you activate a virus that was in your genome,

vertical transmission when your 18 months old, 12 months old, and what’s

vulnerable at that moment in your life is your brain. So,

there’s a lot of work to do down that line.

Then there’s phase one, two, three trials; the subgroups; co-infection work;

and then finally, basically, what’s our long term plan? How are we going to

treat people at different stages of this illness for how long, with what, and so

on?

But hey, we can have some marching orders here. These are things we know how to

do. We’re good at this. This is what’s so much fun is that so many people

know how to do this kind of work. They’re going to be excited to get into it.

So Phase One are those little small trials where we just try it out, there’s

no placebo. It’s mostly a safety study but also an efficacy study. Phase Two

is the next step when you do a bigger study, usually 30-50 people in each arm

and there’s a placebo involved.

(Slide – Clinical Trials)

Phase Three is when you saw Phase Two looked pretty good so you go for it and

you get a lot of money together and

you do studies on 400 to 500 people in each arm.

We have one other little advantage right now, and I hope it will hold up but

right now the FDA perceives Chronic Fatigue Syndrome as an Orphan Disease, an

Orphan Drug Disease. That’s partly (determined) by how many people have it and

they’re saying because less than 200,000 people have been identified with it,

and that’s true, only 15% of patients have been diagnosed, that we will fit

under the Orphan Drug Guidelines, which lets things move a little bit faster,

you can get things out to market without quite as many steps. That would be

good.

(Slide – One do-all design)

This is just one kind of design I threw up here just to show you what people

would think about. I thought this one up and no one’s going to believe me but

I think it’s a great idea which would be an anti-(retro)viral (Group A) on the

top; an anti-(retro)viral with an anti herpes family drug on the middle

(Group C); just the anti-herpes viral drug on another arm (Group ; and then a

placebo on the fourth (Group D). So you’d actually do four arms at once and

answer all the questions in one fell swoop.

There’s a neat anti-herpes family anti-viral that is in a phase three trial

that’s very low toxicity that a company has in California. They just presented

at the infectious disease meeting, their infectious mononucleosis data and it

was really good. So it might be a drug that’s less toxic than the one we

already have (from audience – What drug is it?). It doesn’t have a name yet,

it’s still all numbers. I’ll tell you about it. It’s exciting. So we’ll

see. There’s all kinds of things to think about.

(Slide – What would that take?)

So what is that going to take?

It’s going to take basic scientists and clinical scientists that are working

together doing the in vitro work. Funding. Interested companies that

want to do the big clinical trials. And ultimately, an NIH clinical trials

group to work together to make it happen.

How fast it happens all depends on the money. It always about the money.

Section 8 – Research Funding & Advocacy

(Slide – Sections Overview)

When you get down to it, the reason why this happened this fast is the

Whittemore’s put their own money into it. They didn’t go through the NIH.

Slide – The Importance of Philanthropy

    * This Huge finding was funded primarily through private donations

    * Private donations give the investigator the flexibility to jump on a

finding this important, and not wait the 12 to 18 months required for NIH grant

preparation, submission, review and funding (Though, believe me that this is

happening too!)

I’ve been to their fundraisers, They put on these glorious fundraisers, they

can raise a million

dollars in an evening. It’s amazing. And they raised enough money and put

some people together and in two years they did this work, they didn’t have to

wait for a review process and wait for the cycle, cycle, cycle.

Right now if I wrote a grant today to do this it would be submitted in January,

it would be reviewed in March, it would go to council in July, it would be

funded in September and I would get to start a year from now. So private money

sometimes is the best money, particularly when you’re on the edge of something

really, really big like this.

So certainly, one of the biggest things that going to happen right now is fund

raising, it is going to be private foundation type fund raising. It’s terribly

important. In addition to doing the stuff we’re going to do with the NIH and

all of the other funding from federal agencies that do this kind of thing.

It’s going to be everybody working together.

So, philanthropy is

really important. And I put this slide up, not just for the people in the room

but because we’re putting this video on the web and I am hoping it’s going

to reach a lot of voices.

Slide – Importance of Philanthropy

    * If you were waiting to donate, now is the time – the difference could

be the difference of years until effective therapy strategies are worked out and

in place.

    * Consider:

    * The University of Miami Morton Fund, in memory of Morton who died

as a result of CFS

    * The IACFS/ME research fund

    * The Whittemore- Institute

    * The CAA research fund

    * The ME/CFS Pocket Money Research Fund at www.pocketmoneyfund.org

This is the time to be philanthropic in this disease. This is your moment. This

is the time your dollar makes the biggest possible

difference. Hear me say that never has there been a more critical time to

invest your philanthropic dollar in this disease. We wouldn’t want to you to

take away from some other diseases but do it anyway. Jump Ship. Come on over

because we really need this money right now to do this incredibly important

work.

And we are doing the other important work that it takes to get grants through

the more traditional avenues but that will take time. And time that you guys are

out of. You are ready for this to happen. I know you are. Everyone is begging me

for the next step and we don’t have it because we need to do the science.

So what kinds of places might you put your money?

Slide - Importance of Philanthropy

    * University of Miami Morton Gift Fund

    * http://www6.miami.edu/umgiving

    * Specify the Morton Gift Fund

    * CFIDS

Association

    * Whittemore Institute

    * ME/CFS Pocket Money Research Fund www.pocketmoneyfund.org

Well, I’m going to make a pitch for University of Miami right here and the

Morton Fund (https://www6.miami.edu/campaign/gift...g.html?unit=16). Beth

Goldberg who put all of this together with the help of Pandora

(http://www.pandoranet.info/) and Dan Moricoli. We have a fund called the Morton

Fund, it’s named after a young man that died of Chronic Fatigue related

complications some years back and has been my main research donation tool here

at the University of Miami. There’s also the Whittemore- Institute;

the CFIDS Association has an excellent donation account; the IACFS/ME which is

the professional group that I was president of not very long ago. And then Dan

just put together this pocket fund web-site. A lot of different ways you could

give where it would make a difference.

But do think about that.

I didn’t put on the international links. I meant to do a little research

before I did this but because this is videoed and it will be international I

would ask people internationally to think about their own foundations,

I know New Zealand has a terrific group, the ANZMES group

(http://www.anzmes.org.nz/); Excellent groups in England and Ireland; ME Trust

(http://www.imet.ie/) and others. Barcelona has a fabulous group. There are a

lot of different places where one can put their donation dollars and make a big

difference. And it would be a really good year to make that your plan.

Advocacy

Slide – The Importance of Advocacy

    * No better time than now to let your government (know) that 20 years of

trivializing this devastating illness has stopped and it is payback time.

    * Demand clinical trials

    * Demand serious research funding,

set aside dollars big enough to deal with an illness that has hurt 1 million

Americans

    * Demand private disability companies retract the mental illness

decisions and payback your lost income

In addition to fund raising, now is an awful good moment you advocates. This is

a good time and you are all advocates for your own illness. No better time than

now because you have a passionate story. You’ve spent 20 years with an illness

that’s been basically “blown off†(Audience – 30!). A Long time. So, you

know you are standing in a position where people should feel a little

embarrassed, you know a lot embarrassed, a whole lot embarrassed. Your

government should feel like they have a true obligation. I will say that at that

CFSAC meeting last Thursday and Friday we were getting, people were hearing us.

I think we were really being heard. And certainly, take that all the way; push

it; go to your congress people, OK.

You can only push the NIH, they have their budget and they are told to do every

– they have one pot and everybody wants it and they really can’t be told to

spend it this way or that, they end up having to divvy up one way.

You go to congress, they can actually put aside money and there is one really

important tool they have. There is something called the Office of

Congressionally Mandated Research. This is an Army office. It comes out of the

DOD budget, a very healthy budget one might say. The Office of Congressionally

Mandated Research and that is absolutely the place where advocacy can put real

committed dollars to an illness. Gulf War Illness has that, in fact my research

right now is funded through the DOD, Gulf War Illness, through the Office of

Congressionally Mandated Research. They are wonderful people, they are very

professional, they know how to do peer review properly, they know how to get

money into the hands of people who will

really spent it in a… and boy do they watch how you spend it. The Army -

I’ve never had so much oversight in my budget in my life.

So, sitting in your seat – Are you excited? Yeah, you should be! It is damn

exciting! This is great! This is the good stuff; this is what you’ve been

waiting for (lots of applause – around the world!). I mean really – Yea!

Reply With Quote

And 9

So, there are some issues here. That blood test only identified 67% so if I

ordered a blood test on you right now and it was negative, what would happen to

your soul? You know, and yet it might not really be negative, in fact it’s got

a one chance in three of being wrong. The blood test that we don’t have yet

that we will have very shortly, those tests are going to be improved on.

When the first HIV blood test came out it wasn’t any good either. You know, it

went through stages and stages and stages before we got a really good one.

Don’t rush to get the test. Why, because you’re not going to act on that

test quite yet. The knowledge of being positive is not going to give you an anti

viral prescription from anyone right now because we don’t know which one to

give and if it’s safe or if it’s toxic. The HIV drugs are not been gentle,

OK, and you guys are really tender. So, if you knew your status today it really

wouldn’t change anything.

If they are right 99% of you are positive. And if they are wrong then 95% of you

are positive.

So when? Soon, really soon. But you wouldn’t be able to bear the false

negative right now so be careful OK. There are kits already out there, they want

cash and there’s no reimbursement from your insurance provider yet. I was

talking to this great scientist at the VA and he said, you know, my lab develops

tests. That’s what we do. What’s wrong with the tests you got? Oh, I could

fix that and he got all jazzed and I’m

thinking, damn, get another guy in the field and you know, and he’s fixed

your test, that’s great. So these people, they’re already out there and they

know how to do it and tests will improve.

If you don’t have this virus – what if you didn’t. Well, you know,

that’s good news too because that puts you in a different group and we know

not to do all that toxic stuff to you. So that’s an important thing to do too.

So don’t be discouraged even if you’re negative.

We talked about these other people that might also actually be infected. We

don’t know. These are just people we are going to be looking at. The Gulf War

Illness group I’m desperate to see right away because it could change the

whole direction of that work and they have a fair amount of money to do that

work.

So the conclusion, it really is a big thing. It’s a big thing. You should be

very excited. It’s a very hopeful thing. Yeah, the research is

already underway, more to come. The more we can get funded the more focused and

intense we will be in getting this work done as quickly as possible. That work

we were already doing plays right into this. All the genomics work and all the

immunology work. That is all critical to the better understanding of this

illness and how this virus plays into it.

Those of you that are in my good day bad day study, it’s nice because we’ve

got your stuff already in the freezer and we’ll be looking at this virus as

quickly as we can get access to the assay. That study, that’s a really

important study. It looks at people in relatively better times and worse times

and we’ll know if viral load is causing that. If there’s anything about this

virus. We’re already looking at all the immune parameters and endocrine

parameters and everything under sun. But we’re trying to understand what

mediates relapse.

There are people in this room that have

been in my genomics study where we put people on a bike and made them sick on

purpose and then watched why they got sick. That was a heroic thing to do, we

appreciate it, we’ve learned a tremendous amount from that study. We want to

continue doing that study. We’re fundraising to do the last of the chronic

fatigue group. We’re going to run 15 more chronic fatigue patients and then we

ran out of money. I’m looking to finish that study. You can be sure we’ll

look at viral expression now that we know that we should be looking for viral

expression.

So, all these thing are important. They all tie together,

Section 12

Taking care of yourself

(Question from audience) What is going to give us most bang for our buck right

now. If we’ve got $50…

(Answer) Morton Fund, darling. No seriously, Morton Fund really, really needs

your money. We’re down to the last dollar. The reason why were able to do the

genomic study

is because of the Morton Fund. I was only allowed to do it on the Gulf War

patients and I was able to take just $50,000 and do literally about a half a

million dollars worth of research because I tagged it onto another study that

was well funded.

(Question from the audience) What do you think is the most important thing that

we could be doing for ourselves?

(Answer) There’s some very important things that you can do for yourselves,

OK. And remember that the issues with chronic fatigue syndrome are that sleep is

non-restorative, the immune system is over activated and not working and viruses

reactivate, the endocrine system is acting a little funky and is a little

disregulated and your autonomic nervous system which controls your blood

pressure and pulse and all that is some sort of seesaw yo-yo thing that goes up

and down. And the combination of all that makes you ill.

First you need to , well it’s so simple, eat right. The rule

of exercise – exercise makes you relapse but you can exercise up to the point

of relapse and you’re better than not exercising at all. So, in a global way

the easy way to call it is the five minute up, five minute down rule. You can do

five minutes of something then you got to take a five minute break. Five minutes

then another five minute break. You add it up by fives not 5, 10, 15, 20. 5,5;

5,5; and keep adding fives so you recondition, OK.

Supplements. Supplements are aimed at first, good nutrition, but you are very,

very deficient because you use up stuff very quickly so you use up the B

vitamins and your minerals much faster than the next person. So a good multi

vitamin, maybe double the normal dose of the multi vitamin plus a good B

complex. Omega 3 fatty acids because they are anti inflammatory and quiet tumour

necrosis factor but they don’t do it til you get up into the 4g range so one

of those little caps isn’t enough. You need

to get up to 4, 5, 6.

CoQ10 was anti-fatiguing but it was just the best antioxidant tested. Just

absolutely sucked up all those free radicals better than anything else. They

used a dose of 60 twice a day but they are tiny little people so do the maths

for yourself. If you are twice the size of a Japanese person you might just want

to double up on that CoQ10.

Inosine. There’s a drug called Isoprinosine, Immunovir, that’s a

pharmaceutical grade neutraceutical. Then we presented at the Reno meeting our

own open label work with a hundred patients. And we had a very nice response,

both immunologic and clinical response in the majority, 85% of the patients that

took Isoprinosine which is Immunovir. Now, Inosine is the over the counter

variation on that theme.

If I can go back to sleep for a moment. Non-restorative sleep is a big problem

for chronic fatigue patients. It’s one of the diagnostic criteria. Anyone here

who’s ever had a

restorative night’s sleep with chronic fatigue can tell me that when they do

have a good night’s sleep they do have a better day. What we presented at the

Reno meeting was our own review of charts and found a surprising number of

chronic fatigue patients that develop apnoea over time, sleep apnoea. You’re

so debilitated that you have a disabling fatigue, you have a justification for a

proper sleep study. So I guess the studies.

There’s a drug that’s in clinical trial for fibromyalgia, it’s called

Xyrem. It’s a stage, slow wave sleep inducer and it puts people out very

quickly in just 20 minutes, 10 minutes, sometimes 5 minutes. You take it at the

bedside, you go down to a deep sleep. Now, during deep sleep is when you make

your hormones at night and it’s a really important thing and most of you

don’t have any slow wave sleep. When you get your sleep studies you’ll find

you’ve got none and so inducing slow wave sleep might be

good. Xyrem has had a successful fibromyalgia clinical trial and it is at the

FDA trying to get the fibro label on the drug so that’s probably going to be

the one that’s going to be reimbursable by your health insurance claim.

Reply With Quote

Final section

Question: If you were going to guess on a timetable for, number one, for the

test, when they would have a good test? And, number two, when you would think

they’re going to have a drug that’s going to help the symptoms? If you were

going to guess right now, what do you think the timetable is?

Klimas: Well, number one is easy, I think number one will come very

quickly.

Question: I think six months…

Klimas: Yeah, I think six months is possible.

Question: What about drug therapy/treatment?

Klimas: How fast could you do a Phase I, a Phase II and a Phase III? And,

if we’re considered “orphanâ€, which is the big

if, Phase IIs can, in the “orphan†world, be something called “a II slash

III†[a II/III]. You can start it as a small study and, if it’s looking

good, you can just roll it right on into the Phase III. You can keep on going.

And, the FDA typically requires two Phase III studies for a drug approval - two

years, three years? It could be very quick.

Question: When I fly from north to south, it seems that I really crash

afterwards, I find it really hard to recover from that.

Klimas: You guys are about a litre short in blood volume, ok? If I’m

sitting at five litres, you’re sitting at four. So, you’re really, really

sensitive to blood volume changes. If you’re a little dry, you crash. You’ve

got to hydrate so aggressively when you’re in dry areas.

Question: Unfortunately, I’m not one of your patients. I’ve tried for many

years to get in but…

Klimas: This tells you how terrible this is: I

have a 350 patient waiting list. Ok, and there’s no place else. And, I

can’t practice… I mean, there’s no way to do it all. That’s why, with

the help of Hanna, we were putting together this clinic. A model clinic open in

Kendal – we’re going to have our opening in December. But the point of it

is…

Question: Can I ask something else?

Klimas: Yeah, sure.

Question: Some of us may not be able to afford the clinic. That’s a concern

for me.

Klimas: Right, that’s why we’re growing the University of Miami clinic

at the same time. I’ll just say, I wish I could solve this problem for

everybody. But, at the University of Miami we have very generous patients who

donated a salary line for a physician to do nothing but Chronic Fatigue

Syndrome. Which is amazing! It’s taken us a little while but we have the

doctor hired. She’s going to start in January and we will more than quadruple

the volume of our

clinic here at the University of Miami which takes all insurance.

Question: How can we get into research…

Klimas: Oh, you don’t need to be a patient to be in a study. Studies are

for everybody and you don’t pay to be in a study, in fact, often the study

pays for you.

Let me talk about research for a moment. This tele-health study is a really cool

study. It’s the brainchild of years and years of research where we found that

Cognitive Behavioural Therapy can really help people take control of their

lives. The first studies we did were group therapy here and you had to get here

and some of our patients were too sick to get here. And, we didn’t know

whether or not we could generalize and say: Yeah, it’s great for everybody.

So, we designed this other study and, at home, you take the group on the phone,

it’s a tele-health - they give you this phone and fix you up with a group and

there’s a Cognitive Behavioural

Therapy group on the phone. It’s very neat.

We also have the “Good Day/Bad Day†study I referred to before. I don’t

know who’s here from my group besides Mack, here. We still have room for, I

think, 70 more patients in that study – lots of room. That’s a neat study

because we’re trying to develop bio-markers and we see people four times and

we do these very expensive and comprehensive evaluations with all kinds of

immune and other kinds of lab tests - they’re all yours, free, they pay you

$20 to come.

We have the Gulf War Illness study that has a Chronic Fatigue Syndrome group.

And, that is a genomic study.

So, the point of our group here at the University of Miami has always been to

advance the science. To advance the science, we have to have study subjects and,

frankly, my original reason why I had a clinic was so that somebody was taking

care of people so that I could recruit my studies. But, then I got sucked

in by you all and I love being your doctor.