Alexandra Collin de l’Hortet, PhD, on Evaluating Epigenetic Gene Therapy for the Treatment of FSHD

“The key takeaway is that we can rescue methylation on that particular locus in the genome and that correlates very well and that translates very well into a suppression of the toxic gene target that is the cause of that disease—a complete reduction of cell death or apoptosis and eventually a rescue of muscle function. Those are the key takeaways from the product that starts with the root cause, the methylation, and all of the positive effect that restoring methylation has on that disease.”

Facioscapulohumeral muscular dystrophy (FSHD) is a rare form of muscular dystrophy that currently has limited treatment options and no cure. As such, the unmet need is very great for the approximately 800,000 people worldwide with FSHD. Although aspects of the disease can be heterogeneous, FSHD is linked to muscle wasting caused by overxpression of the gene DUX4, which in turn is thought to be caused by lower than normal levels of DNA methylation in the D4Z4 microsatellite region of chromosome 4.

Notably, Epic Bio is currently developing EPI-321, an investigational epigenetic gene therapy product intended to treat FSHD by restoring methylation of the aforementioned DNA region to normal levels. EPI-321 is a CRISPR-based system delivered by an adeno-associated virus vector and functions by adding a methylation mark. The company recently presented preclinical results obtained in several different models at the American Society of Gene & Cell Therapy (ASGCT) 27th Annual Meeting, held May 7 to 10, 2024, in Baltimore, MD.

At the conference, CGTLive® spoke with Alexandra Collin de l’Hortet, PhD, the head of therapeutics at Epic Bio, to learn more about EPI-321 and the findings that were presented. Collin de l’Hortet explained how EPI-321 targets FSHD, which is epigenetic in nature, and noted that positive downstream effects were observed in patient cell lines. She also spoke about the challenges related to working in FSHD and future plans for the company’s platform.

Click here to view more coverage of the 2024 ASGCT Annual Meeting.

REFERENCE
1. Smith LA, Borrman T, Silvis MR, et al. Validating EPI-321 safety for FSHD: A comprehensive off target characterization platform for epigenetic gene therapies. Presented at: ASGCT Annual Meeting 2024, May 7-10; Baltimore, Maryland. Abstract #258