Gary Owens, MS, on the Potential of ARCUS–Mediated Gene Editing in Duchenne Muscular Dystrophy

“...We show that we transduce and edit PAX7+ cells, which are a marker for muscle satellite cells. Muscle satellite cells are key for muscle regeneration, and a very important milestone, I think, for this dataset. We're super excited to share that with the people here, the physicians, and the patients out [there] that need treatment.”

A seminal moment in gene therapy occurred recently with the FDA’s approval of Sarepta Therapeutics’ delandistrogene moxeparvovec (Elevidys; previously known as SRP-9001) for the treatment of ambulatory pediatric patients aged 4 to 5 years with Duchenne muscular dystrophy (DMD); it was the first gene therapy to be approved for patients with DMD.¹ Despite this great advance, many companies and institutions are continuing to develop novel genomic medicines for DMD in order to provide additional options and address remaining unmet needs for patients with this devastating disease. One such company is Precision Biosciences, which is currently conducting preclinical research with a gene editing platform referred to as ARCUS.

At the American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting, held May 16 to 20, in Los Angeles, California, Gary Owens, MS, the associate director for gene therapy discovery at Precision Biosciences, presented data demonstrating that ARCUS nuclease pairs delivered by an adeno-associated virus vector are capable of excising a “hot spot” region in the dystrophin gene in order to enable production of a functional dystrophin protein in a humanized DMD mouse model.² Pathogenic mutations in the "hot spot" region, which consists of exons 45 to 55, are found in up to 50% of patients with DMD.

In an interview with CGTLive™, Owens discussed the findings he presented and the main implications of the research for the healthcare community. He highlighted that the DMD model mice treated with the ARCUS approach achieved a maximum force output (MFO) in the gastrocnemius muscle that reached 86% of levels seen in healthy control mice, a significant improvement over the MFO seen in untreated DMD model mice.

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REFERENCES
1. Sarepta Therapeutics Announces FDA Approval of ELEVIDYS, the First Gene Therapy to Treat Duchenne Muscular Dystrophy. News release. Sarepta Therapeutics. June 22, 2023. Accessed July 14, 2023. https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics-announces-fda-approval-elevidys-first-gene
2. Lewis W, Owens G, Jordan-Steele M, et al. ARCUS-mediated excision of the “hot spot” region of the human dystrophin gene for the treatment of Duchenne muscular dystrophy (DMD). Presented at: American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting. May 16-20, 2023; Los Angeles, CA.