Two new research projects funded to explore potential treatments for calpainopathy/LGMD2A
$500,000+ committed to gene therapy research since initiative launched in 2017
Coalition to Cure Calpain 3 (C3), a non-profit patient advocacy organization focused on identifying and advancing potential treatments for limb-girdle muscular dystrophy type 2A/calpainopathy (LGMD2A), today announced updates to its Gene Therapy Initiative. C3 launched the initiative in 2017 to accelerate the understanding of the potential of gene therapy to treat LGMD2A by funding research projects testing several approaches.
“Gene therapy has shown tremendous promise in numerous diseases caused by a single malfunctioning gene, including in more common forms of muscular dystrophy and other LGMD subtypes,” said Jennifer R. Levy, PhD, C3 Scientific Director. “Because LGMD2A is caused by a malfunctioning calpain 3 gene, we believe that gene therapy holds great promise to treat this debilitating disease for which there is currently no treatment or cure. Our gene therapy initiative is designed to study a number of gene therapy techniques with the goal of advancing potential treatments toward the clinic as quickly as possible.”
C3 recently funded two new research grants to explore the potential of gene therapy for LGMD2A :
- Isabelle Richard, PhD, Researcher at Généthon in Paris, France will evaluate a novel model of LGMD2A and then utilize it for the development of adeno-associated viral (AAV)-mediated gene therapy. The project, “Calpain and animal models: towards therapy,” will administer calpain 3 gene therapy to the model in order to define the lowest dose needed to effectively improve skeletal muscle function. The project builds on Généthon‘s expertise and focus on developing gene therapy treatments for rare diseases.
- Zarife Sahenk, MD, PhD, Professor of Pediatrics and Neurology at Nationwide Children’s Hospital, in Columbus, Ohio will assess the safety and efficacy of AAV-mediated gene therapy in a mouse model of calpainopathy. Dr. Sahenk recently demonstrated that LGMD2A is associated with impaired muscle regeneration after injury, and this defect can be corrected by injection of the muscle with AAV attached to the calpain 3 gene. In the current project, “Pre-clinical studies for gene therapy in LGMD2A,” Dr. Sahenk will deliver the calpain 3 gene throughout the body of a mouse model for LGMD2A to test the safety and efficacy of this method, and to provide proof of principal data for a potential calpain 3 gene therapy for LGMD2A patients. The Center for Gene Therapy at Nationwide Children’s Hospital has extensive expertise in developing gene therapies for muscular dystrophies and has a stellar reputation for bringing gene therapy to clinical trials.
These grants mark the third and fourth research grants, respectively, that C3 has funded as part of its gene therapy initiative, with a commitment to date of more than $500,000.
In 2017, when this initiative was launched, C3 funded two gene therapy projects:
- “LGMD2A: DNA-Mediated Gene Therapy” led by Michele Calos, PhD, Professor of Genetics at Stanford University is a two-year project testing the delivery of a healthy calpain 3 gene to muscle cells by using DNA. The DNA is injected into the bloodstream and into muscles and taken up by muscle fibers, where the cellular machinery generates the healthy calpain 3 protein. Dr. Calos’ team is evaluating whether the healthy calpain 3 gene is delivered to the muscle fibers. The potential benefits to muscle function are being assessed using a mouse model of LGMD2A.
- “Gene Editing of Calpain 3 in LGMD2A” conducted by Rita Perlingeiro, PhD, the Lillihei Professor in Stem Cell Medicine at the Lillihei Heart Institute at the University of Minnesota, is a 12-month project using the gene editing technology CRISPR-CAS9 to correct mutations in the calpain 3 gene in cells derived from LGMD2A patients. Dr. Perlingeiro’s results will determine the feasibility of a gene editing approach, a different technique than gene therapy delivery, for LGMD2A.
“As our Gene Therapy Initiative research projects near their first milestones, we are excited to soon learn which approaches have the potential to ultimately benefit patients with this serious disease,” says Dr. Levy.