Target: Rogue Immune Cells

Drugs for autoimmune diseases like multiple sclerosis, type 1 diabetes, and rheumatoid arthritis provide relief from symptoms but don’t address causes. Researchers now hope to change that with an emerging class of vaccines made from DNA that shut down the immune cells that go awry in these diseases. Early results have been so promising that human trials for the first treatment-a multiple sclerosis therapy that made paralyzed mice walk again-will begin early next year.

In MS patients, rogue immune cells attack the nerve covering called the myelin sheath, leading to numbness, weakness, cognitive problems, and eventually paralysis. There’s no existing cure; a leading drug, called beta-interferon, regulates the immune system to reduce the severity of attacks but can carry severe side effects. “Treatments today for these types of autoimmune diseases are basically blunt instruments,” says John Walker, CEO of Bayhill Therapeutics, the Palo Alto, CA, startup developing these DNA vaccines. “We’re interested in taking much more of a rifle-shot approach.”

Two engineered DNA molecules make up the vaccine; both are taken up by specialized “first responder” immune cells, which are thus transformed into MS-fighting machines. One DNA molecule encodes a protein found in the myelin sheath; the first-responders make this protein, which acts as bait for the rogue immune cells. Once this trap is sprung, the second DNA molecule goes to work. It encodes a protein that switches the rogue cells from a destructive mode to a protective mode.

Lawrence Steinman, the Stanford University Medical Center immunologist and neurologist who developed the approach and cofounded Bayhill, says the strategy has dramatically reduced the severity of the disease in mice-and even made paralyzed mice walk again. “There isn’t a mouse we haven’t cured,” Steinman says. “Now the issue is, can we translate this into man?”

With 350,000 people suffering from MS in the United States alone, that is a critical question. To begin answering it, the company has raised $14.5 million in its first round of financing and plans to begin human trials of the MS vaccine in early 2004. If all goes well, a vaccine could reach patients in about seven years.

Once the technology is proved in humans, Bayhill plans to develop treatments for other autoimmune diseases. Indeed, the same basic approach has met with success in mouse models of rheumatoid arthritis and type 1 diabetes. New studies are testing whether it may even be possible to reverse existing joint damage. Vijay Kuchroo, a neurologist at Harvard Medical School, believes DNA vaccination “has broad applications” for autoimmune diseases. “I think it has a great future,” he says. While that remains to be seen, the root causes of autoimmune diseases are in researchers’ rifle sights.