Published December 6, 2022
By Bill Bruton
Gil I. Wolfe, MD, SUNY Distinguished Professor and the Irvin and Rosemary Smith Chair of the Department of Neurology, is involved in trials of FcRn (neonatal FC receptor) antagonists that offer a new approach to treating myasthenia gravis (MG).
One of those drugs — efgartigimod — is now approved, and Wolfe and Nicholas J. Silvestri, MD, associate professor of neurology and assistant dean for student and academic affairs, have been using it successfully in patients.
“Myasthenia gravis is the first human disease to receive an FDA approval for this mechanism of action. To date, the trials of these agents, in general, have demonstrated that this mechanism of action can work effectively, quickly and safely in MG, providing us a new avenue of therapy that didn’t exist until last year.”
Wolfe is first author of a paper published in the Journal of the Neurological Sciences titled “IgG Regulation Through FcRn Blocking: A Novel Mechanism for the Treatment of Myasthenia Gravis” that documents the research.
FcRn is critical to maintaining immunoglobulin G (IgG) and albumin levels through rescuing these molecules from lysosomal degradation. IgG autoantibodies are associated with many autoimmune diseases, including MG, a rare neuromuscular autoimmune disease that causes debilitating and, in its generalized form (gMG), potentially life-threatening muscle weakness. IgG autoantibodies are directly pathogenic in MG and target neuromuscular junction proteins, causing neuromuscular transmission failure.
“What this new avenue of therapy provides is a pharmaceutical approach to prominently reduce IgG — it’s not a big procedure like plasma exchange, that requires large-bore catheters and so forth,” Wolfe says. “There’s a lot of interest across many mid-sized to larger-sized pharmaceutical companies, because there are so many diseases that are mediated by IgG.”
“This pharmaceutical approach basically does the same thing as much more invasive procedures: It reduces IgG very quickly and very significantly — by 70 percent — really within days,” Wolfe adds. “This approach has potential applicability across a wide range of immunological disorders both in neurology and beyond.”
Wolfe, named a State University of New York Distinguished Professor — the highest faculty rank in the SUNY system — earlier this year, is an internationally renowned leader in neuromuscular diseases, with a primary focus on MG.
“Myasthenia gravis is really the vanguard disease. For the first time in decades, MG is putting into place a therapy that can have broad implications across many, many human diseases,” Wolfe says. “It’s nice to see the disease I focus on the most having that type of position. We’re informing the potential of therapy for a lot of other diseases, both inside and outside neurology.”