Brain drug target discovery in MS

US researchers have found two potential targets for treating multiple sclerosis after an extensive trawl through proteins in the brain. Comparison of 2,538 proteins from MS patients with those from healthy brains showed damage in two proteins not before linked to the disease. In mice blocking the effects of the proteins led to reversal of symptoms, the study in Nature reported.

There are about 85,000 people with MS in the UK. The condition is caused by a defect in the body's immune system, which turns in on itself, attacking the fatty myelin sheath which coats the nerves, leading to symptoms including blurred vision, loss of balance and, in some cases, paralysis.

Study leader Professor Lawrence Steinman said this was the first large-scale study to search for defective proteins in MS lesions in the brain. They found a few proteins peculiar to MS brain lesions.

But two in particular - tissue factor and protein C inhibitor - showed signs of damage during the chronic active stage of the disease. These normally participate in the control of blood clotting and in anti-inflammatory pathways. The researchers guessed that the damaged proteins might be helping the progression of MS and, by using inhibitors of the proteins found they could successfully ameliorate the disease in mice.

Professor Steinman, from Stanford University School of Medicine in California, said the finding opened up the way for new treatments. However, using existing drugs which interfere with the control of blood clotting would be dangerous because of an increased risk of bleeding.

Professor Neil Scolding, from the University of Bristol Institute of Clinical Neurosciences, said: "From the scientific perspective, the exciting thing is that it's pretty much the first time that proteomics has directly yielded a candidate molecule that is both unexpected and novel on the one hand and has therapeutic potential. From the clinical perspective, showing that treatment approaches predicted by this proteomic interrogation of MS tissue do have a clear impact in experimental models of MS is extremely promising. This points the way to a new area of MS research of considerable interest, and which could well lead in the future to new lines of treatment."

Dr Laura Bell, Research Communications Officer at the MS Society, said she looked forward to seeing how the research progressed. "This is early research but provides an interesting insight into some of the potential players that cause different types of damage to the central nervous system in people with MS. Understanding how MS develops is vital to target therapies for the condition."