Coalition to Cure Calpain 3 Provides Gene Therapy Initiative Updates

WESTPORT, Conn., Sept. 18, 2018 /PRNewswire/ -- 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, scientific director at C3. "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.

About LGMD2A

Limb-girdle muscular dystrophy type 2A (LGMD2A), which is also called calpainopathy, is a progressive muscle-wasting disease caused by defects in the calpain 3 gene. LGMD2A is a rare disease and the most common single form of limb-girdle muscular dystrophy (LGMD), representing an estimated 30 percent of all LGMD cases. It is estimated that LGMD2A affects roughly one in every 43,000 people.

In most cases, LGMD2A patients experience symptoms by age 20. Roughly half of LGMD2A patients experience muscle contractures, which may cause toe-walking and scoliosis. LGMD2A affects large muscles most and results in both weakness and reduced exercise endurance. Eventually, patients have difficulty with daily living activities such as climbing stairs, rising from a chair, or getting up off of the floor. LGMD2A patients typically lose their ability to walk within 10 to 30 years from the first onset of symptoms. Unlike some other forms of muscular dystrophy, heart and lung involvement is fortunately rare, and life expectancy may be near normal.

About Coalition to Cure Calpain 3

Coalition to Cure Calpain 3 (C3), a national, public, 501(c)(3) non-profit organization, was founded in 2010 for the specific purpose of funding research efforts focused on understanding the biology of and finding a cure for LGMD2A/calpainopathy. C3 was created by people with LGMD2A for people with LGMD2A, as both C3 founders have this progressive disease. C3 is motivated by its desire to encourage collaboration among scientists, those who have LGMD2A, their families, friends and the community at large to bring an end to this under-researched, underfunded rare disease. For more information, visit

Jennifer R. Levy, PhD
Scientific Director, C3

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