Maggie is awarded a $1.8 million grant from the U.S. Department of Defense for her study “Develop Novel Podocyte Endoplasmic Reticulum (ER) Calcium Stabilizers to Treat Focal Segmental Glomerulosclerosis (FSGS).”
FSGS is the most common primary glomerulopathy leading to renal failure and disproportionately affects African-Americans, a highly represented population among military personnel and Veterans.
While it is known that podocyte ER stress plays an important role in the pathogenesis of FSGS, there is no treatment to date that targets podocyte ER. Currently, the mainstay of treatment for FSGS is immunosuppressant therapy that does not act on podocytes; in addition, these drugs do not halt disease progression in all patients and they have many adverse side effects.
The grant is based on our study published at PNAS 2019, we have demonstrated that the podocyte ER calcium release channel, type 2 ryanodine receptor (RyR2), underwent remodeling during ER stress, resulting in ER calcium leakage and cytosolic calcium elevation. The leaky RyR2 activated cytosolic protease calpain 2, which led to podocyte injury. Importantly, in collaboration with NIH/NCATS, they also identified a novel chemical compound (NCGC003844) that stabilized the podocyte ER RyR2.
The proposed therapies are pioneering ‘proof-of-concept’ studies that could lead to a significant leap forward in the treatment of military personnel.