Muscular dystrophy is a disease where mutations in the dystrophin gene — key in building and maintaining muscles — harbors a mutation that leads to lifelong muscle degradation. Sarepta Therapeutics, a small biotechnology company, has developed a molecule that allows the cells protein-making machinery to bypass the damaged portion of the gene on its RNA and produce a functional protein, in frame. The company is preparing to submit its drug and clinical trial data to the U.S. Food and Drug Administration (FDA) for approval; the drug has shown positive results in previous clinical trials.

Duchenne muscular dystrophy is a debilitating childhood disease that affects one in 3,500 newborn males. As the dystrophin protein is key in connecting cells of the muscle to the matrix of structural proteins that are outside of the muscle, the lack of a functional dystrophin protein causes muscle cells to die, triggering progressive muscle weakness and severe fatigue.

Dystrophin is the largest single gene in the human body and has 79 exons, or separate coding regions of the gene in the genome. These exons are then essentially strung together when DNA is read and messenger RNA is produced. In the case of Duchenne muscular dystrophy, an exon can be deleted or mutated, and the machinery of the cell cannot go past that point when reading the gene's DNA. This prevents the dystrophin protein from being produced in its entirety.

Eteplirsen targets the 51st exon coding region of the gene, which is present in 13 percent of all cases of muscular dystrophy, and allows protein making machinery in the cells to skip it, while maintaining the proper amino acid sequence of the protein. The company has earlier stage drugs that target exons 45, 50, and 53, and is exploring treatments for mutations contained within all exons found in the disease.

The molecule would allow for skipping of the damaged part of the gene. From:

The submission will take place in the first half of 2014 and follows various meetings with the FDA because this is the first drug of its kind to be used and applied for approval. "We are encouraged by the feedback from the FDA and believe that data from our ongoing clinical study merits review by the Agency and will be sufficient for an NDA filing," said Chris Garabedian, president and chief executive officer of Sarepta Therapeutics. "We plan to work closely with the FDA to prepare an NDA submission in the first half of 2014 as we continue to prepare for our confirmatory study and our manufacturing scale up."

Although the clinical trials showed that children with the disease were able to walk further than they had before beginning their one-hour-a-week intravenous treatment, the company is relying heavily on data showing that dystrophan levels in muscle had increased by 47 percent on average. Another issue is that the clinical trial was small, which may hamper efforts to gain accelerated approval from the FDA. Because lives are on the line and patients with this disease usually do not survive beyond their early 20s, the FDA will have to make some tough decisions concerning this new class of drug and its approval.

GlaxoSmithKline (GSK) is also working on a drug to target exon 51 and is currently in Phase III clinical trials and recruiting patients. GSK's technology is different from Sarepta's, yet results in the same "in frame" skipping of the damaged exon.