A gene therapy has been shown to be safe and effective in treating mice with limb-girdle muscular dystrophy type 2E (LGMD2E). This research has been crucial in advancing to clinical studies, which are due to start in the US later this year.
LGMD2E is caused by mutations in the beta-sarcoglycan (SGCB) gene. This results in a loss of SGCB protein, which is important for the structure and function of muscle.
Dr Louise Rodino-Klapac and Dr Jerry Mendell and colleagues at the Center for Gene Therapy, Nationwide Children’s Hospital, Ohio, USA, have developed a gene therapy that aims to introduce a healthy copy of the SGCB gene into the body. The gene is delivered using an adeno-associated virus (AAV), which can be injected via the bloodstream.
The researchers tested the gene therapy in a mouse model of LGMD2E. These mice lack the SGCB protein and show similar symptoms to humans with the condition.
Delivery of the gene therapy was very efficient and significantly increased the amount of SGCB protein in the skeletal muscle, diaphragm and heart of the treated mice. This resulted in improvements in muscle strength, kyphoscoliosis (curvature of the spine) and heart function. The effect on the heart is particularly important as 50 percent of people with LGMD2E develop a cardiomyopathy.
Mice treated with the gene therapy also showed increased levels of activity and did not tire as easily as the untreated mice. There were no adverse reactions to the gene therapy so the researchers concluded that it was safe.
Dr Louise Rodino-Klapac and Dr Jerry Mendell are working with Myonexus Therapeutics to test this gene therapy – and other LGMD gene therapies – in clinical trials. Myonexus is expected to launch a phase 1/2a trial for people with LGMD2E in the US in November.
This study was published in the scientific journal, Molecular Therapy.
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