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The Patient Leading an Assault on MS

By Catherine Arnst Sometimes it takes an outsider to change the course of scientific research. Scott Johnson, a 49-year-old Silicon Valley entrepreneur, was just 20 when he was diagnosed with multiple sclerosis, an incurable, degenerative disease of the nervous system. By the time he reached his 40s, Johnson walked with a limp and could barely use his right arm. Naturally, he wanted a cure or at least an effective treatment.

MS occurs when out-of-control immune systems attack and destroy myelin, the fatty tissue that surrounds and protects nerve cells. In 2001, a short BusinessWeek article about research into myelin repair caught Johnson's attention. He started attending MS medical meetings and talking to everyone in the field, and decided that it should be possible to coax the body into regenerating myelin. In 2002 he brought together the five top MS researchers in North America, all from different academic institutions. He told them he would start a foundation to fund their research if they would agree to share all discoveries immediately -- an unusual approach in the fiercely competitive world of academic science.

RAISING MILLIONS. The five scientists responded eagerly to Johnson's offer. They knew it would take 15 to 20 years to find an effective myelin repair drug if they continued working alone. By cooperating, they might reach the same goal in five years. "We are all looking at proteins that may be very important [drug] targets but have been overlooked," says David R. Colman, director of the Montreal Neurological Institute of McGill University, and one of the five scientists. "No one lab could do that. It would take an army of people."

Within six months, the Myelin Repair Foundation (MRF) was created. The initial $1 million donation came from Scott Cook, a founder of Intuit, who has a family member with MS. Johnson has now raised $4 million, with a five-year goal of $25 million. And the researchers have already identified more than 50 proteins contained in myelin that might serve. "I think even the scientists are surprised by how rapidly we've moved ahead," says Johnson.

Certainly, the search for a cure for this illness has never moved rapidly or produced many successes. A progressive disease of the central nervous system, MS usually strikes adults between 20 and 40 years of age. For unknown reasons, some 75% of its victims are women, and most live in northern climates. About 2.5 million people worldwide have the disease, with 400,000 of them in the U.S.

HOPE SNATCHED AWAY. MS takes hold when the immune system's T-helper cells, which trigger inflammation, go haywire and attack myelin. This protective coating acts much like the sheath surrounding electrical wires. As the disease destroys more and more of the myelin, nerve signals to the body falter or stop, and patients can suffer from numbness, impaired vision and speech, loss of bladder control, paralysis, and even death.

Patients have few options for treatment. Tysabri, the first new MS drug in more than a decade, was suspended in February just three months after it received Food & Drug Administration approval. The drug, made by Biogen Idec (BIIB) and Elan (ELN), blocks overactive immune cells from entering the brain and attacking myelin. But in ongoing clinical trials, researchers linked Tysabri to a rare and deadly brain disease in two patients.

Scientists speculate that because the drug tampers with immune cells, it may leave some patients vulnerable to brain infections normally kept in check by those same immune cells (see BW, 3/14/05, "The Tricky Biology Behind Tysabri"). Infections present a risk for any drug that modulates the immune system, which explains why the MRF researchers are trying to approach the disease another way.

Scientists already know that healthy cells continuously replace myelin and that even in the early stages of MS, the body can successfully repair the damage. As the disease worsens and attacks on the nerves accelerate, this repair mechanism is overwhelmed. The scientists working with the MRF want to find a drug that can regenerate myelin which, they hope, would greatly limit the ravages of MS.

A NEUROLOGICAL FIRST. Dr. Ben Barres, professor of neurobiology and developmental biology at Stanford University School of Medicine, says his lab has discovered a particularly promising substance, an enzyme that can trigger rapid remyelination in a culture dish. He has already shared this discovery with the other members of the foundation, who are attempting to discover whether the enzyme will perform the same function in animals and slices of brain tissue -- tests that would take years to accomplish if left to one lab.

Barres is quick to point out that this research will likely not lead to a cure. Whatever is causing the immune system to attack myelin in the first place would remain. Still, "a drug that would promote myelin repair would be a quantum step forward," he says. "It would be the first time we are able to promote repair in any neurological disease." As such, the lessons learned may apply to other afflictions that involve myelin loss, such as strokes and spinal cord injuries. Similarly, the MRF's successes with collaborative research could encourage other such efforts. That would come as a welcome change in the lonely world of academic science. Arnst is a senior writer for BusinessWeek in New York

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