C3 recognizes September 30 “Limb Girdle Muscular Dystrophy Awareness Day” with research grant

Coalition to Cure Calpain 3 (C3) is proud to support September 30 “Limb Girdle MD Awareness Day” with the announcement that we are awarding a new research grant to Dr. Michele Calos, Professor in the Department of Genetics at Stanford University School of Medicine, to develop a gene therapy approach in a calpainopathy mouse model using non-viral delivery of plasmid DNA. The project is titled “Calpainopathy: DNA-Mediated Gene Therapy.”

Calpainopathy (also called limb girdle muscular dystrophy type 2A, or LGMD2A) is caused by a mutation that leads to dysfunctional or absent calpain 3. Dr. Calos proposes to introduce a functional copy of the calpain 3 gene into a calpainopathy mouse model by injecting into the bloodstream DNA containing the non-mutated gene. The DNA will then flow out of the microvessels where it will be taken up by muscle fibers. Once inside the muscle cells, DNA will enter the nuclei and express the calpain 3 protein. After various time periods, Dr. Calos’ team will analyze levels of the calpain 3 protein and monitor for potential beneficial effects on muscle structure and function.

The method of gene delivery that Dr. Calos will use employs plasmid DNA, or “naked” DNA. This differs from adeno-associated virus (AAV)-mediated delivery in that it does not require viruses to transport genes to muscle cells. This method has several potential advantages over AAV-mediated therapy, including a lack of immune response (allowing re-dosing if needed), inexpensive manufacturing, and cardiac avoidance.

Dr. Jennifer Levy, C3 Scientific Director, comments, “Gene therapy has tremendous potential to correct calpain 3 deficiency. C3 is proud to support Dr. Calos’ project to develop a method to deliver the gene for calpain 3 via DNA-mediated gene therapy.”

Dr. Calos says, “We are excited to extend our gene therapy studies to address calpainopathy and hope we can make progress that will have a positive impact on LGMD2A patients.”