Chronic Active Lesion Evolution in Multiple Sclerosis

WATCH TIME: 3 minutes

Matthew Schindler, MD, PhD: First, chronic active lesions are an extremely emerging biomarker in multiple sclerosis. There's a lot of research that's been going into them for a number of reasons, so I just like to define it a little bit. So chronic active lesions are based on sort of a histopathological description of having activated microglia macrophages that are at the edge of some MS lesions. So it's a subset of MS lesions.

We recently, in the last decade or so, have developed MRI markers that have a really good radiological histological correlation with these CALs, as we call them, and we call those PRLs, so paramagnetic rim lesions. A lot of work has gone into showing that MS patients who have the presence of these paramagnetic rim lesions have more aggressive disease phenotypes. So they have, on average, greater disability scores and they reach higher disability levels earlier than patients that do not have any evidence for PRLs on their MRIs.

We're just really interested in understanding how these lesions affect patient outcomes over time. It also seems to be quite correlated with, or specific to, MS. If we look at other diseases, including other inflammatory diseases and other mimickers of MS, we don't see these lesions on their MRIs. So, it may actually end up being also a very good diagnostic biomarker. So much of the work is really focused on after they occur—after a CRL or a PRL has formed—and their associations, but we really don't know which lesions will actually form into them. That's important because if we're going to start to try to target treatments against this type of lesion for patients, particularly those that have more of these lesions, we want to be able to predict who's going to develop them and then target our treatments to that population. So that way we're avoiding exposing patients to medicines that wouldn't necessarily target their lesions.

Transcript edited for clarity.