Thursday, January 02, 2003

BY CAROL ANN CAMPBELL
Star-Ledger Staff

A new medicine significantly reduced brain lesions in people with multiple sclerosis and also pushed nearly half of Crohn's disease patients into remission, according to research published in today's New England Journal of Medicine.

In MS and in Crohn's disease, immune cells that should only fight infection instead turn on the body itself, causing havoc. The new compounds, called SAM (Selective Adhesion Molecule) Inhibitors, stop these immune cells from leaving the blood stream and causing inflammation in the nervous systems of MS patients and in the gastrointestinal tracts of people with Crohn's disease.

Although both studies must still be replicated with larger numbers of patients, experts said the new compounds hold great promise in treating MS and Crohn's disease as well as other so-called autoimmune diseases, such as rheumatoid arthritis and ulcerative colitis.

"It is potentially a new way to treat numerous autoimmune disorders," said Paul O'Connor, an investigator on the study and MS researcher at St. Michael's Hospital in Toronto.

The journal reports on two studies using the same compound, which is being developed by Elan Corp., based in Dublin, Ireland, and Biogen Inc., of Cambridge, Mass. It will be marketed under the name Antegren.

In the MS study, 213 patients in the United States, Canada and England were given monthly infusions of Antegren, or a placebo, for six months. Brain scans showed that patients who got the placebo had about 10 new brain lesions during the six months. Meanwhile, patients who received the drug had about one new lesion, or a 93 percent reduction. These brain lesions can affect the ability of MS patients to talk and walk. The disease affects the nervous systems and spinal cords of young and middle-aged adults, and is marked by unsteady gait and fatigue. Those on the drug also experienced 50 percent fewer relapses.

"It's a brand new approach that's been very successful. Time will tell with the results of the next phase of trials, but I do think it has the potential to be a fairly significant step forward," said J. Theodore Phillips Jr., an investigator who participated in the trials at Texas Neurology, a clinic in Dallas.

"We still don't have cures. This is not a cure," he said.

In the Crohn's disease study in Europe, 248 patients with the disease received two infusions a month apart. Half got a placebo. After six weeks, 44 percent of the patients who received only Antegren reported remission, compared with 27 percent in the placebo group. Some 71 percent of patients who got the drug reported feeling better.

"Many of these patients are at the prime of their lives. Some of these patients end up requiring surgery, even mutilating surgery and need to wear colostomy bags. I think this is a significant advancement," said Subrata Ghosh, a Crohn's disease researcher at the Imperial College of London.

"Obviously the disease itself will not go away. But people who go into remission can have a relatively normal lifestyle," he said. Many people with Crohn's are plagued with severe diarrhea, pain, fever and weight loss.

In MS, immune cells migrate to the brain, causing inflammation and destruction of the sheath that insulates the nerves. In Crohn's disease, a similar process of inflammation occurs, but in the gastrointestinal tract.

Antegren binds to a molecule on the surface of immune cells, preventing the cells from leaving the blood stream and migrating to the brain or intestines. The drug is now being tested in studies that will look at 2,000 MS patients, and in studies looking at 850 patients with Crohn's disease.

The two companies paid for the research. Lars Ekman, president of research and development at Elan, said the company hopes to file for U.S. Food and Drug Administration approval by the end of 2003. The company also has begun very early and limited studies testing the drug in rheumatoid arthritis and ulcerative colitis.

Carol Ann Campbell covers medicine. She can be reached at ccampbell@starledger.com or (973) 392-4148.