First-in-human trial demonstrates the safety and feasibility of a heart-targeted AAV gene therapy, with key molecular validation supported by NDRI-sourced human tissue.
Cardiotropic AAV Gene Therapy for Heart Failure: A Phase 1 Trial
Authors: Timothy D. Henry, Eugene S. Chung, Monica Alvisi, Ferzin Sethna, David R. Murray, Jay H. Traverse, Lothar Roessig, Luke Roberts, Swarna Reddy, Youjun Chen, Tugba Guven Ozkan, Stacy Webb, Monika Mittal, Leigh Ervin, Hesham Sadek, Sheila Mikhail, Kobra Haghighi, Canwen Jiang, R. Jude Samulski, Evangelia G. Kranias, Anna P. Tretiakova, and Roger J. Hajjar
Published in: Nature Medicine (2025)
Heart failure remains one of the world’s leading causes of death and disability, affecting an estimated 60 million people worldwide. A new study published in Nature Medicine reports promising results from a first-in-human trial of AB-1002, an investigational gene therapy designed to improve heart muscle function by restoring calcium regulation within cardiac cells.
The multicenter U.S. study, led by researchers from The Christ Hospital and Asklepios BioPharmaceutical, tested a cardiotropic adeno-associated viral (AAV) vector that delivers a gene encoding a constitutively active protein phosphatase 1 inhibitor (I-1c) directly into the coronary arteries of patients with advanced heart failure.
In 11 participants with nonischemic cardiomyopathy and NYHA class III symptoms, a single infusion of AB-1002 was well tolerated, with no treatment-related serious adverse events and preliminary signs of improved heart function and quality of life.
Laboratory analyses provided compelling molecular evidence of the therapy’s biological activity. In tissue obtained from a treated patient, researchers observed gene uptake and restored phosphorylation of a key calcium-regulating protein. To benchmark these findings, control heart tissue from healthy donors, obtained through BioIVT and the National Disease Research Interchange (NDRI) was used for comparison, underscoring the essential role of human biospecimens in translational research.
The results support continued clinical development of AB-1002, which is now being evaluated in a phase 2 trial (GenePHIT).