September 17, 2008

While lesions have long been a hallmark of MS, several types of studies have demonstrated that even areas without lesions (normal appearing brain tissue) are affected by the disease. A new study illustrates how myelin lipid (fat) composition is changed in MS in a way that may destabilize myelin structures. Using post-mortem brain tissue samples, scientists at Johns Hopkins have analyzed the lipid content of myelin found in normal appearing brain tissue in people with MS, and compared it with samples from non-MS subjects.

They found that samples from MS subjects, particularly those where immune cells were present, had a higher phospholipid and lower sphingolipid content than the non-MS samples. Plugging the chemical characteristics of this altered lipid composition into a model showed that myelin layers with this composition would have a greater tendency to repel each other, leading to a less stable myelin sheath.

Sphingolipids can be changed into phospholipids by a series of biochemical transformations. This study did not identify why this process seems to be more active in MS brain tissue, but the authors speculate that enzymes involved in this pathway may be altered due to oxidation. They also note that the lipid mediator S1P may also be reduced because of this increased activity, which is something that the investigational drug FTY720 (fingolimod), a S1P-receptor modulator, may affect in a beneficial way.

Biogen Idec is working on the first experimental drug that may reverse the symptoms of the neurodegenerative disease.

The drug, being tested in animals and prepped for its first human trial, is designed to block a protein called Lingo-1 that interferes with body’s production of myelin, the fatty protective coating around nerve fibers.

No name or code name given in the article, but we'll be watching the progress of this one.