Gene therapy, the use of genetic material to treat a disease or disorder, is making strides in muscular dystrophy. Although the approach is still considered experimental, studies in animal models have shown promising results and clinical trials in humans are underway.

Gene therapy has the potential to help people with inherited disorders, in which a gene mutation causes cells to produce a defective protein or no protein at all, leading to disease symptoms.

To deliver the genetic material to the cells, scientists use a tool called a vector. This is typically a virus that has been modified so that it doesnt cause disease. It is hoped that the vector will carry the therapeutic gene into the cells nucleus, where it will provide the instructions necessary to make the desired protein.

The most common form of muscular dystrophy, Duchenne muscular dystrophy, is caused by a mutation in the DMD gene, which codes for a protein called dystrophin. Dystrophin is part of a protein complex that strengthens and protects muscle fibers. When the cells dont have functional dystrophin due to the gene mutation, muscles progressively weaken. Scientists think that supplying a gene that codes for a functional form of dystrophin might be an effective treatment for Duchenne muscular dystrophy.

Using gene therapy to deliver a correct form of the dystrophin gene has been challenging because of the size of the DMD gene, which is the largest gene in the human genome so it does not fit into commonly used vectors.

Scientists are having more success with a shortened version of the DMD gene that produces a protein called micro-dystrophin. Even though its a smaller version of dystrophin, micro-dystrophin includes key elements of the protein and is functional.

Administering a gene for micro-dystrophin to golden retriever dogs that naturally develop muscular dystrophy showed promising results in a study published in July 2017. Muscular dystrophy symptoms were reduced for more than two years following the treatment and the dogs muscle strength improved. The gene was delivered using a recombinant adeno-associated virus, or rAAV, as the vector.

A similar therapy is now being tested in people in a Phase 1/2 clinical trial (NCT03375164)at Nationwide Childrens Hospital in Columbus, Ohio. A single dose of the gene therapytreatment containing the gene encoding for micro-dystrophinwill be infused into the blood system of 12 patients in two age groups: 3 months to 3 years, and 4 to 7 years. The first patient in the trial, which is recruiting participants, already has received the treatment, according to a January 2018 press release.

The biopharmaceutical company Sarepta Therapeutics is contributing funding and other support to the project.

Sarepta is developing another potential gene therapy for Duchenne muscular dystrophy where rather than targeting the DMD gene that codes for dystrophin, the therapy will be used to try to increase the expression of a gene called GALGT2. The overproduction of this gene is thought to produce changes in muscle cell proteins that strengthen them and protect them from damage, even in the absence of functional dystrophin.

A Phase 1/2a clinical trial (NCT03333590) was launched in November 2017 at Nationwide Childrens Hospital for the therapy, called rAAVrh74.MCK.GALGT2.

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Gene Therapy in Muscular Dystrophy - Muscular Dystrophy News