Uric acid linked to multiple sclerosis.

Mice paralyzed by a disease resembling multiple sclerosis can walk again after receiving daily injections of uric acid, a compound that occurs naturally in the body.

Treatment lessened symptoms and lengthened survival, report researchers from Thomas Jefferson University in Philadelphia. Sixty percent of untreated animals died within 4 weeks of the disease's onset, but almost 90 percent of the mice treated with the highest doses of uric acid were alive 8 weeks later.

"Before the treatment kicked in, the mice had total hind limb paralysis," says immunologist D. Craig Hooper, a coauthor of the study published in the Jan. 20 Proceedings of the National Academy of Sciences. "When we stopped the treatment, they had a little limp."

The mice were given experimental allergic encephalomyelitis (EAE), a mouse disease that causes chronic bouts of paralysis much like multiple sclerosis in humans (SN: 12/6/97, p. 356). Hooper and his colleagues had reported earlier that they could prevent most EAE symptoms by giving mice uric acid before inducing the disease.

Now, the researchers report that uric acid treatment can reverse, not just prevent, the progression of EAE.

The team also found lower amounts of uric acid in 46 people with multiple sclerosis than in 46 people with other neurological diseases. In a review of 20 million Medicare and Medicaid patient records, the team discovered almost no overlap between multiple sclerosis and gout, a disease caused by excess uric acid. The combined evidence suggests a relationship between low uric acid concentrations and multiple sclerosis in people, Hooper says.

In both multiple sclerosis and EAE, the immune system seems to attack the myelin sheath that insulates the nerves of the brain and spinal cord. Uric acid inactivates peroxynitrite, a compound generated by the immune system to combat invading viruses and bacteria. Thus a deficiency in uric acid might lead to attacks on normal tissue.

However, the idea that low uric acid concentrations cause multiple sclerosis is controversial, says neuroimmunologist Henry F. McFarland of the National Institute of Neurological Disorders and Stroke in Bethesda, Md. He adds that accurately inferring disease causes from patient records is hard, particularly for a difficult-to-diagnose disease like multiple sclerosis.

Stephen Reingold, a neurophysiologist at the National Multiple Sclerosis Society in New York, Cautions that "the vast majority of things that work in EAE prove not very promising in multiple sclerosis." Nevertheless, he adds, "this is an intriguing, provocative finding. It needs to be followed up."