A USC-invented vaccine for multiple sclerosis (MS) is about to enter Phase II clinical trials

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A USC-invented vaccine for multiple sclerosis (MS) is about to enter

Phase II clinical trials

http://www.usc.edu/hsc/info/pr/1vol5/526/ms.html

A USC-invented vaccine for multiple sclerosis (MS) is about to enter

Phase II clinical trials, backed by a combined $3.5 million in

funding-including a $1.1 million award from the National Multiple

Sclerosis Society that is one of its largest in recent memory, as well

as $2.4 million from the National Institute of Neurological Disorders

and Stroke (NINDS).

While the vaccine is unlikely to rid patients of their current MS

symptoms, said Keck School of Medicine professor Weiner, chair of

the Department of Neurology and co-inventor of the vaccine, results from

the Phase I study on four patients indicate that it may well be able to

halt the disease in its tracks.

Weiner and former faculty member Correale, now head of neurology

at FLENI, a foundation and neurologic institute in Buenos Aires,

Argentina, that is involved in the fight against neurological diseases,

came up with the idea for the vaccine together some 6 years ago. A

patent is currently pending, and the Phase II trial has an

Investigational New Drug number, which means the Food and Drug

Administration has looked at and approved the trial.

Multiple sclerosis is a chronic and oftentimes progressive and

debilitating condition that affects some 250,000 to 350,000 Americans.

According to the NINDS, physicians diagnose 200 new cases of MS each

week. It seems to be an autoimmune condition, a disease in which certain

white blood cells turn on the body that produces them.

The best current hypotheses say that MS is caused by the body's T-cells

attacking the myelin sheaths that serve as the insulation for the

conduction of electricity and coat and protect the long, delicate axons

of the brain's neurons.

" This vaccine allows the patient's immune system to take control of the

disease, " said Weiner. " At the end of two years of vaccinations, we hope

they will never need treatment again. "

Weiner and his USC colleagues are currently recruiting patients for the

three-year-long trial, in which 40 people with MS will receive the

active vaccine and another 40 will receive a placebo.

Patients are eligible for the trial if they have what is known as

secondary progressive multiple sclerosis-they had periods of both

remission and relapse for some time, and now are experiencing a

significant progression of the disease (though they may still be

symptom-free at times). They also must be between 12 and 65 years of age

and be able to walk at least 50 feet, though use of a cane or walker is

acceptable.

" It's a very hard task to take sick patients and ask 40 to get a placebo

and go off everything else, " Weiner admitted. " But we think it's worth

it because of the potential benefits of this vaccine. " In addition, he

noted, most of the patients in this trial will likely be treatment

failures on the limited number of treatments available for MS, and so

abandoning those treatments should not be detrimental.

Patients accepted into the trial will have a baseline MRI to measure the

MS lesions in their brains, and then will undergo a process called

leukapheresis, in which their white blood cells are removed from their

body. (Since the body is continually producing white cells-and in fact

will replace the ones removed within 24 hours-this does not have any

long-term effect.)

To create an individualized vaccine, the research team will then expose

those cells to myelin from a cow brain, which should prompt the

characteristic MS response from the misguided, autoimmune T-cells. (The

cow brains have been examined for any evidence of the so-called mad cow

disease-bovine spongiform encephalopathy-in collaboration with Nobel

laureate Stanley Prusiner of the University of California, San

Francisco, and have been approved for use in the preparation of these

vaccines.)

Those T-cells are then exposed to 12,000 rads of radiation, killing them

and at the same time altering them subtly, so that when they are

reintroduced into the body, they will be seen as foreign. That

reintroduction-or vaccination-should prompt the immune system to create

antibodies and reactive T-cells against the MS-causing T-cells. " We

vaccinate them against their own bad T-cells, their own bad

lymphocytes, " Weiner explained. " After that, they should be immune to

the cells they produce that attack their white matter at any time in the

future, because they have a memory for the bad T-cells. "

How will this help the patient? Simply put, if the body destroys the

autoimmune T-cells before they can get to the myelin, this

sometimes-devastating disease should be stalled in its tracks. " We don't

anticipate that it will get anyone out of a wheelchair, " said Weiner.

" But we think we can prevent the progression of the disease. We will

have made their immune systems 'normal' again, leaving the future repair

of their nervous system an easier task. "

Vaccines will be created for both the vaccine and placebo groups. If the

trial shows that the vaccine is useful, it may be possible to then

vaccinate the placebo group as well.

Weiner is optimistic about the vaccine's chances.

" We're giving them weapons to kill their self-immune responses, which

you and I can do on our own. In the vaccinated patients, the good

T-cells are interacting with the bad T-cells and killing them. "

The patients will receive vaccinations every month for three months, and

then every three months for two years at the General Clinical Research

Center, an NIH-supported facility at LAC+USC Medical Center. The third

year of the study will simply be follow-up, to see whether the effects

of the vaccination persist over time.

The vaccine will be deemed successful if it can halt the progression of

existing lesions and the appearance of new MS lesions, as measured by

MRI. Weiner and his colleagues will also look at any changes in

neurologic function and will be monitoring any and all side effects of

the vaccine.

From a scientific point of view, Weiner noted, the study will most

likely put the lid on the debate over whether myelin is indeed the

immune system target in MS; scientists have long assumed that to be the

case, but it has yet to be definitively proven.

An even more interesting question that the trial will address, he noted,

is just how the immune system is able to get quite so out of control,

spewing out the literally self-destructive T-cells at an ever-increasing

rate.

" The implications of this trial are really quite interesting, " said

Weiner. " We've made a case that this is worth doing scientifically.

Overall, I think this trial is very exciting for USC, especially since

the vaccine was invented, developed and manufactured here. "

by Lori Oliwenstein

http://members.cox.net/marty.altman/Page%20-%20MS%20Cure.htm