Marjan Gharagozloo, PhD: Preventing CNS Inflammation and EAE Onset

“The interesting part was that the group that did not develop spontaneous EAE had some level of subclinical inflammation when we looked at all their cytokines and molecules.”

It is well known that an innate immune response plays an important role in driving both the early and later phases of multiple sclerosis (MS), however, there is little effect from the currently used MS therapies on central nervous system inflammation.

As such, Marjan Gharagozloo, PhD, a scientist in the department of immunology at the University of Sherbrooke, and her colleagues believe that the anti-inflammatory molecules which the central nervous system cells express in response can serve as therapeutic targets for the prevention of MS. They hypothesized that Nlrx1, a mitochondria-located innate immune sensor that ubiquitously expressed and inhibits the NF-κB signaling pathway, could inhibit inflammation in the central nervous system and ultimately, the onset of spontaneous experimental autoimmune encephalomyelitis (EAE).

To test this, they generated a new mouse model of MS by crossing Nlrx1^-/- mice with myelin-specific TCR transgenic mice, as the resulting progeny are genetically susceptible to spontaneous EAE. To find out more about their research NeurologyLive spoke with Gharagozloo at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) 2019 Forum in Dallas, Texas.

REFERENCE

Gharagozloo M, Mahmoud S, Simard C, et al. The Mitochondrial Innate Immune Sensor, NLRX1, Inhibits Early Stages of CNS Inflammation and Prevents the Onset of Progressive EAE. Presented at: ACTRIMS Forum; February 28 to March 2, 2019; Dallas, TX. Abstract #3442. actrims.confex.com/actrims/2019/meetingapp.cgi/Paper/3442. Accessed March 20, 2019.