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Gene Therapy Strategy Regenerates Heart Muscle Cells in Pig Trials

By BiotechDaily International staff writers
Posted on 03 Mar 2014
Findings of a preclinical study have shown the effectiveness of new gene approach to regenerate heart muscle in large lab animals following a heart attack.

The research was led by Dr. Hina Chaudhry, founder of VentriNova, and director of cardiovascular regenerative medicine at Icahn School of Medicine at Mount Sinai (New York, NY, USA). In the study, not only did the treated heart tissue regenerate, but the researchers saw evidence of the formation of new heart muscle cells, along with a significant improvement in the heart’s pumping function.

The study was published February 19, 2014, in the journal Science Translational Medicine. The investigators evaluated their gene therapy in pigs as porcine cardiac anatomy and physiology is nearly the same as humans. They administered a gene therapy vector carrying cyclin A2 one week after a myocardial infarction to the experimental group and a null vector to the control group. VentriNova (New York, NY, USA), a regenerative medicine company, is the developer of the gene therapy approach.

The study revealed that the group treated with cyclin A2 demonstrated substantial improvement in cardiac contractile function six weeks later with cellular evidence of cardiac muscle cell division and evidence of new cardiac muscle cells being formed adjacent to the injured heart tissue. Furthermore, research of adult cardiac muscle cells isolated and placed in petri dishes demonstrated complete cell division with preservation of the contractile units of the heart muscle cells in the daughter cells. 

“To our knowledge, this is the only regenerative strategy thus far able to actually create new cardiac muscle cells in the diseased heart of a large animal closely mimicking humans. This approach may have the potential to revolutionize therapy for patients suffering from heart attacks by possibly reversing cardiac damage,” said Dr. Chaudhry.

Dr. Chaudhry is a named inventor on patents relating to methods to prevent heart degeneration. VN-100, the company’s lead product, is a viral vector-based gene therapy that induces cardiomyocyte division in adult heart tissue by delivery of cyclin A2, which is encoded by the gene (CCNA2) that instructs embryonic heart cells to divide and grow, and is typically silenced in mammalian hearts after birth. 

Because the CCNA2 gene is silenced, adult heart muscle cells cannot divide readily to repair and regenerate following a heart attack. Delivering cyclin A2 into the heart following a heart attack has now been shown to reverse cardiac damage by stimulating growth of new heart muscle cells. A series of Investigational New Drug (IND)-enabling studies have begun, and this article marks the fifth scientific publication supporting the potential of this approach.

VentriNova is a preclinical stage cardiac regenerative gene therapy company that specializes in the reversal of cardiac damage by triggering intrinsic repair pathways to generate de novo heart muscle cells. The company’s science and technology is focused on development of biologic and small molecule regulators of the cyclin A2 gene—the key switch mediating heart cell division. This technology has demonstrated that modulation of the cyclin A2 gene stimulates endogenous growth of new heart muscle cells (myocytes) and significantly enhances cardiac contractile function in both small and large animals. 

Related Links:

VentriNova 
Icahn School of Medicine at Mount Sinai
 


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