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From Gout Culprit to MS Treatment?

19 March 1997 (All day)
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Gout and multiple sclerosis (MS) may seem worlds apart, but researchers may have found a beneficial connection between the two disorders. A new study indicates that uric acid--a compound that builds up in tissues in people with gout--prevents paralysis and death in mice with lesions resembling those seen in human MS. The findings, reported in the current issue of the Proceedings of the National Academy of Sciences, suggest that this unlikely potential drug might someday be used to treat a condition that in the United States currently afflicts some 300,000 people, most of whom are between 35 and 65.

People with MS--a mysterious degenerative condition characterized by muscle weakness and, in advanced cases, paralysis and mental problems--have nerve-cell lesions in the brain and spinal cord containing high levels of the neurotransmitter nitric oxide (NO). Thinking that high concentrations of the corrosive NO might play a role in the nerve damage, Hilary Koprowski and his colleagues at Thomas Jefferson University in Philadelphia tested in mice three compounds--uric acid, PTIO, and D609--that are known to scavenge NO or inhibit its production.

They first injected a fragment of myelin protein into the brains of the test mice, causing nerve damage similar to that seen in MS patients. Normally, paralysis sets in within 2 weeks, and the mice die within 3 weeks. Koprowski's group found that daily injections of 20 milligrams of uric acid prevented paralysis in the mice; the other drugs warded off paralysis for only a few days. Some scientists speculate that low uric acid levels may even play a role in the disease. "The idea that a decrease in some normal chemical in the body could cause MS is a new concept," says neurologist Mohamed Rostami of the University of Pennsylvania.

Because uric acid is not a foreign compound to the body--it's a metabolite of caffeine and other purines--Koprowski thinks it makes an ideal potential drug. "You aren't bringing in some outlandish new substance or drug," he says. "You just increase the natural levels in the body." Other experts are more skeptical. "There are many things that have worked in [the mouse model] that haven't worked in MS, or have only modest effects," says neurologist Robert Lisak of Wayne State University in Detroit. Koprowski says his group plans to investigate whether MS sufferers have lower uric acid levels than healthy people and whether gout patients have a lower MS incidence.

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