September 2, 2010

The University of California San Francisco has a substantial MS research program, with particular strengths in genetics and imaging. Scientists from both of these disciplines recently collaborated on a project to learn more about the role of inherited gene variants in MS. In addition to influencing who gets MS and who doesn't, genes may also affect the course or severity of disease, but this aspect of MS has not yet been as extensively explored.

This project focused on the role of glutamate. Glutamate plays an important role in nerve signal transmission in the central nervous system, but it can be harmful to cells if concentrations are too high. Normally oligodendrocytes help to regulate glutamate concentrations by taking in excess glutamate, but this process is impaired in MS, and past research has documented elevated levels of glutamate in MS brains.

The imaging researchers scanned the brains of 382 MS subjects using spectroscopy, which measures the level of different molecules in tissue. The geneticists performed a genome-wide genetics screen on the same subjects. The team then analyzed the genetic results with respect to the glutamate levels determined by spectroscopy. They found several variants in genes associated with glutamate biology that were more common in subjects having the highest concentrations of glutamate. Further analysis showed similar genetic associations in subjects with higher brain atrophy (shrinkage) and lower concentrations of a molecule found in axons (N-acetylaspartate).

These results suggest that inherent genetic differences in nervous system biology among people with MS may influence concentrations of glutamate within the central nervous system, which may then affect survival or death of axons. It is encouraging to see scientists from different disciplines coming together in MS research, because looking at a question from more than one angle can lead to a much better understanding of the disease.