Research horizons: news from clinical trials for chronic-progressive MS.

Betaseron is approved for use in people with relapsing-remitting MS; the trials that led to its acceptance did not include anyone with any other form of MS. Now, Copolymer I and Bioferon are in their final stages of testing--again, in people who have relapsing-remitting disease only.

But there is some hopeful news on the horizon for people with chronic-progressive MS too...

* Methotrexate may slow down progressive MS for some people. Researchers at the Cleveland Clinic, led by NMSS grantee Dr. Donald Goodkin, tested weekly treatments of methotrexate in pill form on 60 volunteers. This drug has a long history of use in treating rheumatoid arthritis and cancers; in the low dose used for MS in this two-year study, it caused no significant side effects.

Methotrexate lowers the number of immune cells in the body, including T cells which orchestrate immune system activity. Only a small subgroup of T cells is generally believed to trigger myelin destruction in MS, but methotrexate sweeps out friendly cells as well as those that may contribute to MS.

When patient records were unlocked and analyzed, 83 percent of the group taking a dummy drug had worsened; but only 52 percent of those on methotrexate had worsened. People who were more disabled at the start of the study did better with treatment than those who were less disabled, and people who developed their progressive MS after having relapsing-remitting disease seemed to benefit the most. Good results were confined to the function of arms and hands.

The National MS Society's Medical Advisory Board calls this study "promising". The next step? Longer, larger studies, to learn more about this strategy.

* Cladribine (2-CdA, commonly known by its brand name Leustatin) is also already in use to treat hairy-cell leukemia. Like methotrexate, it suppresses immune activity. Investigators at Scripps Research Institute in California studied it in 55 people with chronic-progressive MS.

After one year, the group taking cladribine had slightly improved scores on a standard disability test while people in the control group worsened. But there were potentially serious side effects. Moreover, one person on the drug died of hepatitis (not however, clearly related to treatment) and two others developed herpes zoster.

The NMSS Medical Advisory Board cautions that more data are needed: A larger study using a lower, hopefully safer dose and more standard evaluation methods is being planned.

* BetaKine, a newly developed agent made by Celtrix Pharmaceuticals, has entered the first, or safety, phase of trials required for FDA approval. BetaKine is an engineered match for human TGF beta-2 (or transforming growth factor beta-2)--a member of the cytokine family. This group of molecules, produced by immune cells, turns up or tunes down immune system activity. (Beta interferon is another member of the family.)

The strategy here is not to reduce the T-cell population but to interfere with immune cell communication, including the T-cell signaling that may set an MS attack in motion.

The trial at the National Institutes of Health is studying 9 people with active chronic-progressive MS but larger trials may begin as early as this winter if the agent appears safe.

* Peptides--specially shaped protein fragments--may also be able to block crucial events in an MS attack. They jam the T-cell signal recognition system by fitting into selected receptors (or signal receivers) on the surface of T cells, thus making these receptors inactive. The San Diego Regional Cancer Center has initiated safety tests for peptides developed by its research team.

Ten volunteers with either chronic-progressive or relapsing-remitting MS were selected for this trial after tests showed that T cells with specific receptors were in their spinal fluid.

Meanwhile, researchers at Oregon Health Sciences University and the Immune Response Corporation are doing safety tests for other peptides designed to block still other T-cell receptors.

People who volunteered for these trials were accepted only if they proved to carry genes for target T-cell receptors. Some, but not all, people with MS have these genes.