New cancer drugs show potential against MS.

The search to control cancer has produced 2 new and different approaches that may one day improve treatment of both relapsing-remitting and progressive MS.

MS is not cancer, but both diseases seem to involve failures of the immune system to perform as it was meant to. In the case of cancer, immune surveillance fails to destroy cancer cells. In MS, immune surveillance wrongly targets myelin, the special material that protects nerve fibers in the central nervous system. Researchers in both fields have looked to basic immunology research for better understanding of immune system function--especially the many roles played by white blood cells called T cells and the antibodies produced by white blood cells called B cells.

Matrix metalloproteinase inhibitors

These compounds, called MMPIs for short, show promise in cancer treatment. Currently, Marimastat, an MMPI made by British Biotech Pharmaceuticals, Ltd., is being tested in large multicenter clinical trials in Europe. Several thousand people with various cancers are receiving Marimastat, which is MMPI BB-2516.

In the meantime, Dr. Wolfgang Liedtke and 1996 Dystel Prize winner Dr. Cedric S. Raine began work on MMPIs for MS at Albert Einstein College of Medicine in New York. They gave MMPI BB-1101 to lab mice with EAE, which is a model of human MS. The treated mice were healthier, had fewer relapses, and less scarring and myelin destruction in their spinal cords.

MMPIs appear to inhibit the action of enzymes that are needed to ferry T and B cells through the protective blood-brain barrier and into the central nervous system. Recent research has suggested that interferon-B (available as Avonex or Betaseron) also inhibits the activity of these same MMP enzymes.

The MMPIs may do more. Dr. Liedtke and Dr. Raine looked at the impact of the same MMPI on a group of T cells from human beings with MS that have a natural aggression toward myelin. In test tubes, MMPI BB-1101 was a powerful inhibitor of destructive actions by these T cells. The data were published in a paper in the Annals of Neurology last July.

Clinical trials of a similar MMPI in people with MS may begin, but only if the pilot human safety study, now in progress, provides a green light.

Novantrone (or mitoxantrone HCl for injection)

Another anticancer drug, marketed in the U.S. as Novantrone, is currently approved to treat one kind of adult leukemia or, in combination with corticosteroids, to treat pain in advanced prostate cancer. A trial of Novatrone involving 188 volunteers with secondary progressive or relapsing-remitting MS has been completed in Europe.

In both forms of MS, Novantrone appears to reduce the number of attacks, limit the number of lesions or damaged areas in the brain, and slow down progression of disability. This drug apparently works by killing both B and T white blood cells. People in the trial received IV infusions of an inactive placebo or the real drug, at 2 different doses, once every 3 months for up to 2 years.

These hopeful results are tempered by the experience of cancer patients taking Novantrone for more than 2 years. Extended use can lead to significant heart toxicity. At this point, it is unclear how long the drug can be given safely to people with MS.

What happens now?

No one yet knows if either of these 2 new drugs has benefits that outweigh the risks. No one knows if either can be used instead of or along with currently approved MS drugs. Current and future clinical trials will attempt to establish the facts.