Brain scans show interferon slows MS attack.

By documenting changes in the brain with magnetic resonance imaging (MRI), neurologists have gathered evidence that a genetically engineered drug slows the progression of multiple sclerosis (MS).

Last week, an advisory panel of scientists recommended 7 to 2 that the Food and Drug Administration approve a form of beta interferon for treating people with relapsing-remitting MS, which affects up to two-thirds of the 300,000 U.S. residents with the disease. They suffer from unpredictable flare-ups that cause vision problems, memory loss, tremors, partial paralysis, and other neurological symptoms. Often, the disease gradually worsens to a chronic, debilitating stage as it destroys more and more tissue in the central nervous system.

While several medications alleviate some symptoms, this interferon is the first drug deemed capable of slowing the frequency of acute attacks, says Stephen C. Reingold, vice president for research and medical programs at the National Multiple Sclerosis Society in New York City It may work by countering other immune system activity directed against the myelin sheath that coats nerve cells.

In a three-year clinical trial, researchers said, 338 volunteers at seven U.S. and four Canadian research centers injected the drug or a placebo into their leg muscle every other day Neither the patients nor the doctors treating them knew whether they were taking the active drug. The participants kept daily diaries and visited the doctors whenever flare-ups occurred. They also underwent periodic MRI scans of their brains.

Participants taking high doses of beta interferon went an average of 295 days before their first flare-up, 142 days longer than those not on the drug. They averaged 0.84 attack per year, and about 31 percent had no attacks during the study. Those taking the placebo averaged 1.27 attacks per year, and just 16 percent of them suffered no flare-ups during the three years. Participants taking the drug also required fewer trips to the hospital and suffered fewer severe attacks, says neurologist Donald Paty, the study coordinator at the University of British Columbia in Vancouver. The most common side effects were flu-like symptoms and pain from injections.

FDA analysts point out that excluding patients whose attacks were not immediately verified by physicians and those who left the study early weakened the statistical significance of the results.

But MRI brain scans showed that the diseased area increased about 20 percent in MS patients taking the dummy drug but only about 7 percent in those taking moderate levels of the drug; it decreased 4 percent in those taking high doses. "This will be the first time that MRI has shown a real correlation with clinical outcome," Reingold says.

That helped convince the expert committee. "The MRI data make [the study] much more compelling and approvable," says Sid Gilman, a neurologist at the University of Michigan in Ann Arbor.

Reingold expects that clinical tests of new drugs for MS will rely increasingly on MRI evidence. Many neurologists have preferred to monitor participants' health and the development of symptoms, arguing that symptoms are what need treating. But symptoms sometimes disappear naturally or do not show up during a drug trial. "[This study] verifies what a lot of us have expected-- that the MRI would prove to be the most sensitive way to evaluate treatment," says William A. Sibley at the Arizona Health Sciences Center in Tucson.

"If you can treat the [nerve damage], then you're treating the disease," adds Reingold.

Berlex Laboratories of Richmond, Calif., and Chiron Corp of Emeryville, Calif., developed the drug, called Betaseron. Other researchers are testing different interferon products against MS as well.