Biology of a Multiple Sclerosis Drug
In patients with multiple sclerosis (MS), the immune system attacks the central nervous system. This causes inflammation that damages myelin—a fatty, insulating layer around nerve cells—in the brain and spinal cord.
A drug called Tecfidera can be effective in treating MS, but scientists aren’t sure how it works. Now, a team of researchers has uncovered a mechanism that might explain it. Their study appears on the cover of the March issue of the journal Brain.
The lead authors were Dr. Achilles Ntranos from the Corinne Goldsmith Dickinson Center for Multiple Sclerosis at the Icahn School of Medicine at Mount Sinai, who worked for two years at the Advanced Science Research Center (ASRC) at The Graduate Center, CUNY, and Dr. Patrizia Casaccia, founding director of the ASRC’s Neuroscience Initiative and co-director of the Icahn School of Medicine/CUNY inter-Institutional Center For Glial Biology. The team included ASRC Core Facility Directors Jia Liu and Ye He, and research assistant Valentina Bonnefil.
Healthy T cells are part of the immune system, but in an MS patient, T cells appear to attack the myelin that coats nerve cells. Fumaric acid esters, which are involved in cell metabolism, seem to change that T cell behavior. Patients who received fumaric acid ester treatment had lower numbers of brain-targeting T cells than those who did not.
But how exactly does it work? The study found that fumaric acid esters cause epigenetic changes to some T cells’ DNA. In other words, the esters can turn certain genes on and off without changing the underlying genetic code. As a result of these changes, patients treated with fumaric acid esters have lower numbers of immune cells with the ability to damage myelin in the central nervous system. This, the researchers say, is likely how Tecfidera works.
The results could have implications for future therapies for MS as well as other immune-mediated diseases such as psoriasis and systemic lupus erythematosus.
“This work has given us extremely useful insight into how we might leverage the metabolic-epigenetic interplay between cells and their environment to create new immune-modulating therapies for diseases like MS,” said Casaccia, director of the ASRC’s Neuroscience Initiative.