Robert Zivadinov, MD: The Key Question from the TOPIC Study

Robert Zivadinov, MD, a professor of neurology at the University of Buffalo: So the key question now, after the study has shown that [Aubagio reduces cortical grey matter volume loss], is how Aubagio was able to accomplish this task. Certainly, we need to understand better what's going on. As you know, Aubagio has a dual effect on T cell as well as B cell immunity - probably the B cell immunity is much more related to the development of cortical pathology. It is well known that there are lymphoid germinal centers in the meninges of [multiple sclerosis] patients, which are contributing to so-called cortical subpial lesions.

The cortical atrophy is highly related to the development of the cortical lesions in the brain, and particularly, those lesions that are invisible on conventional MRI, which we call cortical subpial lesions. They are not inflammatory and are situated in the third layer of the cortex. So usually, because they are not inflammatory, any anti-inflammatory therapies have no effect on these lesions, so to find that with Aubagio we found an indirect, at least, effect - because we didn't look at the cortical lesions, but we looked at the consequence of cortical lesions, which is the development of cortical atrophy - is very encouraging.

In terms of how Aubagio can really accomplish this, I think, one way could be the B cell story. The other possibility could be an antiviral effect against the Epstein-Barr virus. The Epstein-Barr virus is probably the main contributor, as we’ve published in a number of studies, to the development of cortical atrophy in patients with MS. So now this work is not done. We need, hopefully, to get further and understand whether Aubagio can alter the humoral response to the Epstein-Barr virus, and maybe that would be one of the mechanisms that can explain these results.