RE: More expedient cures

[Guest guest]

Ben,

Thanks, what a great article! I have an important question, What treatment

is Mr. on for his MS??????????

-----Original Message-----

From: [mailto:evansbenjamin@...]

Sent: Wednesday, September 29, 2004 12:41 PM

low dose naltrexone

Subject: [low dose naltrexone] More expedient cures

It looks like science has stopped dragging it's feet on possible cures.

Grant givers are stipulating the work they support be shared more quickly

when discoveries are made; thus taking many years off the standard process.

Hallelujah!!

This story was on the front page of the Wall Street Journal and the first

story is about MS research God bless, Ben

Anxious for Cures,

Grant Givers Turn

More Demanding

To Speed Discovery Process,

Scientists Must Share Data

As Condition for Funding

An Ex-CEO Tackles His Illness

By SHARON BEGLEY

Staff Reporter of THE WALL STREET JOURNAL September 29, 2004; Page A1

Trent Watkins had just made an extraordinary discovery. The young graduate

student had identified a rogue enzyme that could be a key to treating

multiple sclerosis, the neurological disease that can leave victims blind

and unable to walk.

If Mr. Watkins had been conducting science-as-usual, no outsider would have

learned of his " eureka " for years, as it wended its way through scientific

review to publication in a top journal. Instead, within days of the finding,

his lab shared the data with four research groups at other universities. Two

of them quickly set to work on blocking the enzyme in mice and human brain

tissue to see if that would protect the nervous system.

" My heart almost stopped, it's so against how we usually do things, " says

Ben Barres, a Stanford University neurobiologist and head of the lab where

Mr. Watkins is pursuing his doctorate. " Normally, the kind of work we do

would go for seven or eight years before moving to an animal model, which

would take several more years before moving to human tissue. "

The Stanford group reached out to other scientists for one reason: It was a

condition of a grant from a new research foundation that is supporting the

lab's work. Without assurance that Prof. Barres and his colleagues would

quickly share important findings with other scientists, the foundation

wouldn't have written the check.

The requirement reflects a growing movement among patient-advocacy and other

private funding organizations -- ranging from the powerhouse Juvenile

Diabetes Research Foundation to newcomers like the J. Fox Foundation

for Parkinson's Research -- to shake up the structure and culture of

biomedical research. Fed up with the glacial pace at which new discoveries

become medical treatments, the groups are insisting that the scientists they

fund swear off secrecy in favor of collaboration.

Traditionally, academic biomedical researchers get federal grants and tenure

by working largely alone toward basic discoveries, usually collaborating

only with colleagues in their own labs. Now some are calling that model

flawed. Despite the flood of new knowledge in the biosciences, there has

been " a slowdown instead of an expected acceleration in innovative medical

therapies reaching patients, " says Janet Woodcock, an acting deputy

commissioner at the Food and Drug Administration.

What's needed, many agree, is more " translational " research to turn

fundamental discoveries into practical treatments. And funding organizations

are realizing that translational research is by its nature collaborative. A

lone genius might find a disease-causing gene, for example, but turning that

into a cure requires biologists to figure out what the gene does and

chemists to work with them designing drugs to block that action.

Even the National Institutes of Health, the primary funder of basic

biomedical research in the U.S., is beginning to put more weight on

translational research as part of a " road map " unveiled in September 2003.

In addition to funding projects scientists dream up on their own, the NIH is

setting more of its own big goals and directing scientists to work toward

them.

There isn't any assurance that the new strategy will work. It may not

shorten the time required for clinical trials of new drugs or devices, for

instance, which typically take a decade or more. Many scientists say the

traditional system is working fine. Siphoning money -- public or private --

away from basic research and setting direction from above could choke off

discoveries that underpin every treatment and drug now in use, they say. It

could also stifle the independent spirit that leads talented people to

academia in the first place.

But funders say they're tired of writing checks for research that doesn't

lead anywhere. Five years after the juvenile-diabetes foundation raised and

distributed millions of dollars for basic-science research in a 1990s

campaign called " The Only Remedy Is a Cure, " it had no real clinical

progress to show for the money. In one instance, a foundation-supported

scientist discovered a gene that increases the risk of developing juvenile

diabetes. All well and good, says Insel, the foundation's executive

vice president for research, " but then the scientist, being a geneticist,

went and looked for another risk gene. " The first discovery just sat there

in a scientific paper.

" We used to leave it to chance that someone would pick up on the discovery

and advance it, " says Dr. Insel. That has seldom happened. The foundation

distributes more than $100 million a year in research grants but the

scientists it funds haven't found a cure for an illness that afflicts at

least 1.3 million adults and children in the U.S. and 5.3 million

world-wide.

An Active Role

This spring, the foundation began taking a much more active role in some of

the research it supports. It listed steps deemed crucial to treating or

curing juvenile diabetes, such as coaxing the body's insulin-making cells,

which are destroyed in the disease, to regenerate. Then it invited

scientists to propose experiments toward achieving those steps. It also

began requiring that scientists seeking its money either hook up with

researchers from other disciplines or let the foundation play matchmaker --

or look for funding elsewhere.

Left on their own, says Dr. Insel, " academics aren't skilled at translating

discoveries into cures. It's incumbent on us to figure out how to do that,

and it's only going to work if we take a hands-on approach. "

The Fox Foundation for Parkinson's disease, only four years old, also

started out the old-fashioned way, inviting scientists to propose studies

that promised a better understanding of Parkinson's. " But then we looked

around and asked how we could have the biggest impact, " says Hood,

director of the group's research programs. Its answer: Identify specific

advances that will likely help patients and ask scientists to propose ways

of making them happen. " We've become more a partner than just a funder, "

says Ms. Hood.

, a longtime Silicon Valley executive who started the Myelin

Repair Foundation, decided to go even further. In 1976, when he was 20, he

was diagnosed with multiple sclerosis. In this disease, the immune system

attacks the fatty sheath that coats axons, the long cables that carry

electrical transmissions from one neuron to the next. Without this sheath,

called myelin coating, electrical current leaks and the neuronal signal

peters out before it reaches its target. As a result, patients can suffer

extreme fatigue, blindness, loss of balance, slurred speech and problems

with cognition.

After years of consulting and running start-ups, among them a company that

developed technology to destroy air pollutants, Mr. found it more

and more difficult to function with his MS. Today, his right hand is

virtually useless and he walks with a cane. Three years ago, he decided to

pursue a cure full-time.

A Handful of Scientists

In February 2002 he attended a research conference in Ventura, Calif., on

myelin. While Mr. found the studies presented in formal sessions

interesting, he hit paydirt chatting up the scientists in hallways and at

the bar of the Ventura Beach Hotel. If you had to choose just a handful of

scientists to receive funding for research on MS, he asked about 30 of them,

whom would you pick? The names of the same five scientists came up again and

again.

Mr. invited the quintet to a meeting over Memorial Day weekend 2002.

In the boardroom of Silicon Valley Bank in Santa Clara, Calif., he presented

his vision. Repairing myelin, he said, is a " finite and definable " goal for

MS therapy. He was prepared to raise significant sums for such research, but

there was one condition.

Mr. had come to realize that scientists typically keep their

discoveries secret for years, the time it takes to methodically repeat an

experiment to make sure the results are sound, write up a description of the

methods and results, submit the manuscript to a scientific journal, wait for

it to be critiqued, make the requested revisions, resubmit it, and wait some

more until the journal publishes it. In the kind of research he was prepared

to bankroll, the scientists had to agree to work as a team to develop and

execute a coordinated research plan. Anyone who made a discovery had to

share it with the other four labs right away.

That flew in the face of the culture of academic biomedicine and its reward

system. Scientists earn prestige, tenure and more grants by making basic

discoveries, and by doing it first. Being part of a collaboration can dilute

prestige. As a result, scientists typically do not share their hunches or

plans with people outside their own research group. Although studies may

list a dozen authors from several institutions, in many cases the scientists

did not actually work together. They just supplied materials (anything from

lab mice to biochemicals), for instance, or did a statistical analysis of

the data.

" 'Can you send me your reagent and I'll put your name on the paper?' --

that's what counts as collaboration in the usual model, " says neurobiologist

of Case Western, one of the five scientists invited to Santa

Clara by Mr. . " It was very hard to get used to this way of doing

things. "

Laying Out a Plan

Despite some qualms, all five scientists Mr. recruited decided to

take the plunge. They agreed on what should be accomplished by the end of

the first year, " and from that we laid out a business plan, " says Mr.

, who holds a masters in business administration from the University

of California, Berkeley. He and the scientists spent the next six months

refining that plan, scheduling monthly teleconferences and four-month

reviews where the researchers would share results. Starting with a $1

million donation in March from Cook, co-founder of software publisher

Intuit Inc., Mr. established the Myelin Repair Foundation. It has

raised about $2 million toward its five-year goal of $25 million.

The five universities employing the scientists in the collaboration have all

signed intellectual property agreements under which any royalties from

discoveries funded by MRF will be shared 50-50 with the foundation, which

would plow the earnings back into more research grants.

Last November, when the five foundation scientists met in Chicago,

Stanford's Prof. Barres shared his lab's latest discovery. He explained how

Mr. Watkins, the graduate student, was examining rodent brain cells growing

in lab dishes when he saw something striking. Usually, special cells in the

nervous system called oligodendrocytes slather myelin on axons, which is

exactly what MS patients would love to happen in their own bodies. But when

a certain enzyme is present, Mr. Watkins noticed, these special cells fail

to do their job. They sit right next to axons that need myelin but don't do

anything about it. The Stanford group figured that blocking the enzyme might

unleash myelination and maybe heal MS patients.

If he had held back the discovery until it could be published in a

scientific journal, says Prof. Barres, " it would have been years and years

before anyone got around to the next logical step " -- seeing what happens in

lab mice in which the myelination-blocking enzyme is knocked out -- " and

only years after that would anyone get to doing this with human tissue. "

Instead, revealing the unpublished discovery was like shooting off a

starter's pistol. A molecular geneticist at the University of Chicago said

he had mice with an MS-like disease and would see what happened when he

blocked the rogue enzyme. Case Western's Prof. said he had human

brain tissue from MS patients that he would test. " You wouldn't hear this

stuff anywhere else, " says Prof. . " We're thinking about it

immediately, which has probably saved us two years. "

Since then, the Stanford scientists have gone on to identify a molecule that

knocks out the myelination-blocking enzyme and are preparing to file for at

least one patent on it, in the hope that it might be the basis for a new

myelin-repair drug.

On the Trail

At the most recent meeting of the five teams of Myelin Repair Foundation

scientists, ideas flew through the air. Neuroscientist Popko of the

University of Chicago described another molecule that seems to knock out the

myelin-making oligodendrocytes. Now the foundation's team is on the trail of

ways to sideline that molecule.

Prof. unveiled unpublished discoveries about ways to manipulate

precursor cells in ways that make them develop into oligodendrocytes. " The

brain and spinal cord contain these precursor cells, so why don't they turn

into oligodendrocytes? " he asked. Whenever a precursor cell interacts with a

certain molecule, it seems to develop into a kind of cell that is no good at

myelination. By tying up the molecule, precursor cells might take the path

to becoming oligos.

The scientists' goal is to identify a drug target and find a promising

compound by 2009 -- 10 years to 15 years faster, they say, than the

traditional approach. Even then it would take a decade or more to test the

new drug. And only 8% of compounds that enter human trials become approved

drugs.

Mr. is convinced that the hard-driving style he used at his

start-ups is the way to cure the disease that is crippling him. " To make

progress against this disease, " he says, " you have to do things

differently. "

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