Could a heart damaged by disease or cardiac arrest be coaxed to repair itself?
Hina Chaudhry, MD, is leading research of a gene therapy that has shown promising results in animal studies. She co-authored a study published today in Science Translational Medicine that details how the gene, cyclin A2, helps cardiac muscle cells – cardiomyocytes – undergo cell division in pigs, regenerating healthy tissue and helping the heart to repair itself. Normally the cyclin A2 gene is silenced, preventing further cellular division, post-birth in mammals.
The procedure is backed by the biotech company VentriNova, Inc., a TEDMED 2013 Hive company founded by Dr. Chaudhry, who is also a TEDMED Innovation Scholar.
The company claims that no other regenerative strategy on the market or in clinical development has the ability to grow new heart muscle cells in the diseased heart.
“Everybody else has been doing something different — injecting stem cell transplants in the heart, and it has generally failed. You have to understand how cells divide. Why do they stop? That’s where you see the vast mortality of heart disease,” Chaudhry says.
Though there is some rate of cell turnover in the human heart, it is not enough to repair muscle damage after a cataclysmic event such as myocardial infarction. Instead, scar tissue forms. Certain metazoan species, though, do have the ability to regenerate; the newt can replace injured body parts, and the adult zebrafish heart may be able to regenerate up to 20% of its volume, the study reports.
Chaudhry’s team used an adenovirus to deliver cyclin A2, a cell cycle regulatory gene, which induced cell mitoses. Animals that received therapy showed improved heart function compared to controls. The authors also observed significantly decreased fibrosis and increased numbers of cardiomyocytes.
Dr. Chaudhry, who is Director of Cardiovascular Regenerative Medicine at Icahn School of Medicine at Mount Sinai in New York, has been working on the project for close to two decades; she got the idea working as a research fellow.
“This is the most exciting publication of my life,” she said to TEDMED. “I can’t wait until it goes into clinical trials, and I’m very hopeful that it will work in human patients.”
Study co-authors are Drs. Scott Shapiro and Amaresh Ranjan, also from Mount Sinai.
— Stacy Lu