While its potential has been discussed and studied for decades, 2017 was a year that showed the promise of gene therapy becoming a reality for patients. The FDA approved the first gene therapies in the United States for certain rare types of cancers and for a form of inherited blindness. Additionally, a number of clinical trials were recently initiated to test the safety and effectiveness of gene therapies in a variety of diseases including Duchenne Muscular Dystrophy and Limb Girdle Muscular Dystrophies (LGMDs) Type 2B and 2D.

In light of these exciting advances and the potential for gene therapy to make a meaningful difference in the lives of patients in our community, C3 has launched a Gene Therapy Initiative to accelerate development of these therapies for Limb Girdle Muscular Dystrophy type 2A (LGMD2A)/calpainopathy!

Gene therapy is the delivery of a healthy gene to a patient to treat a disease that is caused by a defective gene. The healthy gene is delivered by inactive viruses, or by non-viral methods such as DNA. For LGMD2A, gene therapy would deliver a healthy copy of the calpain 3 gene in order to compensate for the defective version of this gene. Another method, called gene editing, would correct the defective portion of the gene in its native location. Gene therapy manufacturing is complex, requires a high level of expertise, and follows very strict guidelines in order to maintain the quality and safety of the product.

C3 is taking a comprehensive approach to accelerate the understanding of the potential of gene therapy to treat LGMD2A by funding projects testing several techniques. In 2017, we announced the funding of two gene therapy projects:

1. LGMD2A: DNA-Mediated Gene Therapy is led by Dr. Michele Calos at Stanford University. This two-year project tests the delivery of a healthy calpain 3 gene to muscle cells by using DNA. The DNA will be injected into the bloodstream or muscles, where it will be taken up by muscle cells. Inside the muscle fibers, the cellular machinery will generate the healthy calpain 3 protein. Dr. Calos’ team will test if the healthy calpain 3 gene delivery reaches the muscle fibers. The potential benefits to muscle function will be assessed using a mouse model of LGMD2A.
2. Gene Editing of Calpain 3 in LGMD2A is being conducted by Dr. Rita Perlingeiro at the University of Minnesota. This 12-month project uses 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 for LGMD2A.

The C3 Gene Therapy Initiative seeks to accelerate the understanding of gene therapy as a treatment for LGMD2A by funding the research of multiple gene therapy approaches. If results from any current or future Gene Therapy Initiative research projects are positive, they can be progressed towards the initiation of clinical trials for LGMD2A patients. Bringing a therapy from the research lab to a clinical trial is a long and expensive process. C3 is currently funding early stage projects to answer critical questions about effectiveness and safety, which must be established before gene therapy can be tested in patients. In addition to gene therapy, C3 will continue to explore and fund other approaches that could lead to therapies that can slow the progression of the disease or cure LGMD2A.

Gene therapies are currently in trials for other forms of muscular dystrophy and we believe in their promise to potentially cure LGMD2A. Lisa Straface, mother of LGMD2A patient Matt Straface, says, “I am extremely grateful [that researchers] are taking the time to study and focus on calpainopathy.  They are seeing progress in fighting this muscular disease, which gives me hope that eventually there can be a cure or even just a slowdown of this progressive debilitating disease.” Please help C3 fund additional projects to evaluate and accelerate gene therapy approaches for LGMD2A patients!

• Visit and subscribe to the C3 NEWS PAGE which is frequently updated
• Pursue genetic testing to confirm your diagnosis AND join the LGMD2A GLOBAL PATIENT REGISTRY. An accurate diagnosis and the LGMD2A registry are critical to the planning and conduct of clinical trials in LGMD2A
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