Jonathan W. Weinsaft, MD, Future Research With Gene Therapy for Cardiovascular Disease


The chief of cardiology at Weill Cornell Medical College shared his outlook on the future of gene therapy research in the field.

“As we get better at genetic characterization, including whole exome sequencing, and understanding the contributions of polygenic alterations,the interaction between genotype and phenotype, by that I mean people with a given genetic predisposition, who were exposed to an inciting factor environmentally. Soall of these things are going to feed our understanding of how disease progresses and develops and will allow us to target given underlying mechanisms.”

Gene therapy research is expanding to fields such as cardiology, in which gene editing therapy recently made a splash at the American Heart Association’s (AHA) Scientific Sessions 2023 in November. The meeting featured promising data from the phase 1b heart-1 clinical trial (NCT05398029) evaluating Verve Therapeutics’ VERVE-101, an investigational gene-editing therapy intended to treat heterozygous familial hypercholesterolemia (HeFH). Investigators observed dose-dependent decreases in blood PCSK9 and blood LDL-C percentages from baseline with a manageable safety profile and continued dosing at that time.

Since then, Verve has paused enrollment in heart-1 in consultation with the study’s independent data and safety monitoring board (DSMB) after the sixth participant treated experienced asymptomatic grade 3 adverse events and is prioritizing its second generation preclinical therapy, VERVE-102, for the same indication.

CGTLive® spoke with Jonathan W. Weinsaft, MD, chief of cardiology and professor of medicine at Weill Cornell Medical College, to learn more about the potential of gene therapy for cardiovascular disease and his outlook on future research.

1. Vafai SB, Gladding PA, Scott R, et al. Safety and pharmacodynamic effects of VERVE-101 an investigational DNA Base editing medicine designed to durably inactivate the PCSK9 gene and lower LDL cholesterol – interim results of the phase 1b heart-1 trial. Presented at: AHA Scientific Sessions 2023; November 10-13; Philadelphia, Pennsylvania.
2. Verve therapeutics announces updates on its PCSK9 program. Verve Therapeutics. April 2, 2024. Accessed April 2, 2024.
Related Videos
Nathan Yozwiak, PhD, on Researching AAV Gene Therapy Delivery to the Brain
Salvador Rico, MD, PhD, on Informing Clinical Trials With Natural History Studies in Dravet
Zheng-Yi Chen, DPhil, on International Collaboration on Clinical Trials
Janice Chen, PhD, the cofounder and chief technology officer of Mammoth Biosciences
Sekar Kethiresan, MD, on Following up VERVE-101 With Next-Generation Editing Therapies
Maria Escolar, MD, the chief medical officer of Forge Biologics
Leigh Ramos-Platt, MD, on Allowing Access and Ensuring Preparation for Gene Therapies
John Murphy, PhD, the chief scientific officer of Arbor Biotechnologies
Erika Fullwood Augustine, MD, MS, the associate chief science officer of the Kennedy Krieger Institute
Maria Escolar, MD, the chief medical officer of Forge Biologics
© 2024 MJH Life Sciences

All rights reserved.