Advances toward personalized medicine in MS

People with MS who decide to start or change a disease-modifying therapy have a lot of options to consider. That's a good thing, of course, but unfortunately there's not much guidance to predict which therapy will be best for them. However, progress is being made on this topic. Two recent studies have identified gene variants which are associated with response to two different MS therapies. One study examined variations of the genes encoding two proteins (called "ATP-binding cassette-transporters") that affect how long mitoxantrone persists in cells. People with MS who had received mitoxantrone and were assessed for clinical response were tested for these variants. Those subjects who had the variants associated with longer mitoxantrone persistence in the cells tended to have better clinical response, on average (85% were responders vs. 63% for the lower-persistence group). Those variants were not associated with major side effects such as cardiotoxicity, however. Perhaps future studies will find ways to help predict who is at most risk for those serious negative effects.

The second study took a similar approach with interferon-beta, only it examined 61 variants in 34 different genes. People who had either responded or not responded to IFN-b were tested for these genes, and a computer model searched for combinations of variants that were associated with drug response. Two combinations had the best association: JAK2-IL10RB-GBP1-PIAS1 and JAK2-IL10-CASP3. Similar studies have addressed this question previously and have come up with alternative genes associated with IFN-b response. It's unclear how close we are to a predictive genetic test, but hopefully it is getting nearer.