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DNA Vaccine May Stop MS

In Early Test, Multiple Sclerosis Vaccine Turns off Harmful Immune Response
By
WebMD Health News
Reviewed by Louise Chang, MD

Aug. 13, 2007 - A new kind of vaccine promises to halt the destructive immune responses behind multiple sclerosis, type 1 diabetes, and other autoimmune diseases.

Thirty patients already have received four injections of the MS version of the vaccine in a phase 1 clinical trial. The vaccine was very safe, at least in the short term. And there was tantalizing evidence that it just might work.

Hideki Garren, MD, PhD, is one of four Stanford University researchers who invented the vaccine and co-founded Bayhill Therapeutics to develop it. Garren notes that MS is an autoimmune disease in which a specific kind of immune cells -- T cells -- attack nerve cells.

"Our vaccine is designed to go only after the disease-causing cells in MS and leave the other T cells alone," Garren, now Bayhill's vice president of research, tells WebMD. "The first advantage of this approach is we should have fewer side effects than current MS drugs. And second, this should modify the underlying disease because we are going after the disease-causing cells."

In MS patients, T cells attack the myelin sheath that protects nerve fibers. One of the T cells targets is a specific myelin protein -- an antigen -- called myelin basic protein or MBP.

The new vaccine is made of genetically engineered DNA that encodes MBP. Normal vaccines provoke immune responses against the antigens in the vaccine. But the Bayhill vaccine attaches the MBP DNA to a "backbone" cleverly designed to turn off immune responses instead of turning them on.

Sure enough, the vaccine did not make any of the patients' MS worse. In fact, MRI scans suggested that the treated patients had fewer MS brain lesions than those who got inactive placebo shots.

"We did see a trend in reduction of lesions," Garren says. "But these are just trends. Certainly this needs to be tested in larger trials."

Garren's team has just completed a phase II trial in which 290 patients received 13 doses of the vaccine over one year. They plan to report the results in October at a large European MS conference.

Emory University immunologist Brian D. Evavold, PhD, says the new vaccine definitely has an effect on the immune system. Evavold, an MS researcher, was not involved in the Garren study.

"To have antigen-specific targeting that turns off anti-myelin T cells is the Holy Grail of MS research," Evavold tells WebMD. "With a DNA vaccine you can do very targeted changes to the immune system. This would be a huge advance over what we can do right now."

"What WebMD readers can take from all this is that the future is very promising for new MS therapies," Garren says. "Many new drugs are in the pipeline and will soon be available. I would ask MS patients to keep an eye out for our vaccine because of the advantages it has."

If the new approach succeeds, it has implications far beyond MS. Evavold notes that many other autoimmune diseases -- such as type 1 diabetes, myasthenia gravis, and rheumatoid arthritis -- are caused by misguided immune cells.

The trick, Evavold says, is finding the specific antigen to which the T cells respond. Such antigens already are known for type 1 diabetes and myasthenia gravis. Indeed, Garren says his team has already begun a phase I trial of a DNA vaccine for type 1 diabetes. Those results won't be in for a year at least.

Garren and colleagues report the findings in the advance online edition of Archives of Neurology.

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