First-in-Human AAV Gene Therapy for MYBPC3-Related Heart Disease Shows Promise

NEW ORLEANS, LA — Nov. 08, 2025 — Results from the first-in-human clinical trial using AAV gene therapy to treat a specific type of heart disease—MYBPC3-related hypertrophic cardiomyopathy (HCM)—show that the treatment is safe and effectively increases levels of a key heart protein. This advancement may ultimately help improve heart structure and function in affected patients, according to data presented today at the American Heart Association’s (AHA) Scientific Sessions 2025 in New Orleans.

The findings from the MyPeak-1 Phase 1b/2 clinical trial, sponsored by Tenaya Therapeutics Inc., were presented during a late-breaking science session at the conference and simultaneously published in Cardiovascular Research.

A Novel AAV Approach for a Genetic Cause

The investigational treatment, named TN-201, is a first-in-class AAV-based gene therapy. It is designed to target MYBPC3 gene mutations, the most common genetic cause of HCM. HCM is a complex disorder that causes thickening and stiffness of the heart muscle, affecting an estimated one in 500 people.

Six adult patients with significantly enlarged hearts participated in this first phase, receiving a one-time infusion of the AAV treatment—three at a lower dose and three at a higher dose. The patients were monitored for up to a year.

“These initial results are promising for a patient population that is too often misdiagnosed and live with difficult, even dangerous, symptoms,” said Milind Desai, M.D., M.B.A., Director of the Hypertrophic Cardiomyopathy Center at Cleveland Clinic and an investigator for the trial. “In the past decade, we’ve made great progress in understanding and treating hypertrophic cardiomyopathy, and we’re pleased to be potentially advancing it further as we continue to research this AAV gene therapy.”

Safety Profile and Molecular Effect of the AAV Vector

The trial demonstrated that the AAV gene therapy was mostly safe, with side effects being mild, temporary, and easily managed. Cardiac testing confirmed that the AAV vector successfully reached the heart cells and worked as intended, resulting in increased target protein levels and measurable thinning of the heart wall.

Two patients experienced laboratory abnormalities that resolved under hospital monitoring without resulting in symptoms. Immune-suppressing drugs, administered to prevent a reaction to the AAV delivery, were successfully tapered off in the months following the infusion.

Researchers noted that while the obstructive form of HCM has a recently approved disease-specific medication, the non-obstructive form, which is more common in MYBPC3-associated HCM, lacks targeted treatments, underscoring the high unmet need for the TN-201 AAV gene therapy.

Of note, while the U.S. Food & Drug Administration has placed a clinical hold on the trial to address protocol adjustments and minimize variabilities across sites, the hold is not related to any new safety events concerning the AAV-delivered treatment. Researchers caution that these initial findings, while encouraging, mandate further research before the AAV gene therapy can be widely adopted.