Parent Project Muscular Dystrophy (PPMD) has awarded a $239,000 grant to Dr. Terence Partridge, Professor of Systematic Integrative Biology, Research Center for Genetic Medicine at Children's National Medical Center. This grant will help Dr. Partridge and his team continue their work in understanding exon skipping technology for future trials in Duchenne.

Exon skipping is a promising treatment for Duchenne, with the first FDA accelerated approval in Duchenne recently received by Sarapeta Therapeutics for their therapy Exondys 51. Exon skipping uses antisense agents that specifically skip mutated parts of the gene to prevent disruption of production of the dystrophin protein.  Dr. Partridge aims to gain a better understanding of how these agents work in cells to obtain information that will be used to optimize exon skipping therapeutic development.

“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

“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.  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.”

-- Dr. Partridge

Dr. Partridge and his team will test three different antisense oligonucleotide chemistries in two different versions of the mdx mouse, a milder phenotype and a more severe phenotype which is more representative of Duchenne in humans. Through this series of tests, the team will characterize the dynamics of what happens between administration of the antisense agent and the production and maintenance of dystrophin within the muscle fibers.

Specifically, they will look at:

• efficient delivery of the antisense agent into the muscle myonuclei
• the persistence of these agents within the muscle
• efficiency of production and longevity of the exon-skipped transcript
• the rate of synthesis of the dystrophin protein and how long it lasts within the muscle

The team hopes to identify any areas where optimization of the therapy could occur, and hopes to make exon skipping more efficient in the future. 

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