PPMD Awards $239 to Research Effort to Improve Exon Skipping as DMD Therapy

The nonprofit Parent Project Muscular Dystrophy (PPMD) has awarded $239,000 to Dr. Terence Partridge, with the Research Center for Genetic Medicine at Children’s National Medical Center. The grant will support ongoing work aimed at a better understanding of exon skipping therapies for Duchenne muscular dystrophy (DMD), and their validation in future clinical trials.

DMD is caused by mutations in the dystrophin gene that result in the absence of essential muscle protein dystrophin, important to maintaining the muscle fiber cell membrane.

Among many different therapeutic approaches for DMD, exon skipping, mediated by antisense oligonucleotides, is one of the most promising for restoration of dystrophin expression. The first accelerated approval granted by the FDA for an exon skipping treatment for DMD was given to Sarapeta Therapeutics’ Exondys 51 (eteplirsen) in September.

With the new award, Dr. Partridge and his team will work toward understanding how exon-skipping treatments work in cells. The knowledge will be used to boost the clinical development of exon skipping therapies.

“PPMD was excited to learn more about the work Dr. Partridge and his team at Children’s National are doing. It is important to support work that aims to better understand therapies so that our community can participate in clinical trials that are safe and reflect the latest technology. Given the recent accelerated approval of Exondys 51 and the ongoing potential of exon skipping as a therapy for Duchenne, this work is even more important,” Abby Bronson, PPMD’s senior vice president of Research Strategy, said in a press release.

“Exon skipping is the most promising approach that I have come across as a means of treating Duchenne, but has the problem that it is less efficient than we would like it to be.  We think that the best way of achieving this is to identify the weak points in the process and attack them individually,” Dr. Partridge said. “This generous funding from PPMD comes at an opportune moment, when we have just developed and validated a good system for conducting such an analysis.”

The team will test three antisense oligonucleotide agents in DMD mouse models with a mild disease phenotype, and in models with a more severe disease phenotype that is representative of human DMD.

Researchers aim to better understand the underlying process between the administration of the antisense agent and the production of the dystrophin protein, as well as its longevity within the muscle fibers.

They also aim to identify areas where optimization of exon-skipping therapy could occur, with the goal of making these agents more effective.

DMD is the most common neuromuscular disorder of childhood with an incidence of 1 in 3,500 live male birth.