Coalition to Cure Calpain 3 (C3) is delighted to announce a newly-funded research grant to develop a gene therapy for LGMD2A/R1 using vectors optimized for gene delivery to muscles most affected by the disease. This work involves a multi-lab collaboration between Dr. Melissa Spencer at the University of California Los Angeles and Drs. Jeffrey Chamberlain and Stephen Hauschka at the University of Washington. C3 funding for this project supplements grant support the group received from the National Institutes of Health.
“C3 believes in the promise of gene therapy for LGMD2A/R1 because it is a single-gene recessive disorder and thus amenable to gene replacement strategies,” explains C3 Scientific Director Dr. Jennifer Levy. “However, previous work has revealed that cardiac expression must be avoided for this treatment to be safe. This collaborative project brings together investigators with expertise in LGMD2A/R1 and gene therapy vector development to develop an approach that is tailored to the unique features of this disease.”
Previous work has shown that the gene for calpain 3 can be expressed at high levels in skeletal muscle without toxicity, a finding which makes LGMD2A/R1 gene therapy a realistic goal. However, there are unique considerations related to specific features of LGMD2A/R1 that warrant careful development and assessment of gene therapy vectors for this disease. Of particular concern, expression of the gene for calpain 3 in the heart is toxic. Experiments in this proposal will optimize new vectors that are highly selective for all types of skeletal muscle. The new vectors will then be tested in an LGMD2A/R1 mouse model and assessed for toxicity and therapeutic efficacy.