Tuesday, October 31, 2006

Methylthioadenosine Effective in Animal Models of Multiple Sclerosis

NEW YORK (Reuters Health) Oct 19 - Methylthioadenosine (MTA), an adenine nucleoside produced from S-adenosylmethionine, is effective in animal models of acute and chronic multiple sclerosis (MS), according to a report in the September issue of the Annals of Neurology.

"A cell compound such as methylthioadenosine is able to modulate the immune response, and it might become a useful therapy for autoimmune diseases with less toxicity than other drugs because the cell has several mechanisms to compensate its excess," Dr. Pablo Villoslada told Reuters Health.

Dr. Villoslada and colleagues from the University of Navarra, Spain studied the effects of intraperitoneal MTA in rodent experimental autoimmune encephalomyelitis (EAE, a model of MS) and in peripheral blood mononuclear cells from multiple sclerosis patients and healthy controls.

In the acute model, the authors report, MTA on the same day as induction of EAE prevented acute encephalomyelitis in 5 of 10 Lewis rats, whereas 9 of 10 placebo-treated animals developed neurological symptoms of acute EAE.

In rats with ongoing chronic-relapsing EAE, MTA also improved histological findings and decreased the rate of second relapse, the results indicate.

MTA treatment significantly attenuated the proliferative response of rat splenocytes to myelin basic protein and phytohemagglutinin, the researchers note, and had similar immunomodulatory effects on peripheral blood mononuclear cells from rats and from patients with MS.

"MTA would be an excellent candidate drug to be tested in patients with MS because it is safe and is effective in preventing brain autoimmune attack," the authors conclude.

"In addition," they write, "because MTA may have a pleiotropic mechanism of action in preventing T-cell activation, which is a critical step in autoimmune diseases, but without inducing immunosuppression, it appears an ideal candidate for combining with other immunomodulatory drugs to obtain a higher efficacy in stopping relapses and disease progression without increasing side effects."

Because the mechanism of action is immunomodulation by preventing T cell activation, "our target will be other autoimmune diseases and transplant rejection," Dr. Villoslada added. "We have preliminary data suggesting positive effects in type 1 diabetes and rheumatoid arthritis animal models."

Ann Neurol 2006;60:323-334.