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Regenerating heart muscle with gene therapy

VentriNova, a regenerative medicine company with a novel gene therapy product, has announced that the journal Science Translational Medicine has published the results of a preclinical study demonstrating the ability of VN-100 to regenerate heart muscle in large 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. 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 entitled “Cyclin A2 Induces Cardiac Regeneration After Myocardial Infarction Through Cytokinesis of Adult Cardiomyocytes,” was published in the latest issue of the journal Science Translational Medicine.

The investigators tested their gene therapy in pigs as porcine cardiac anatomy and physiology is almost identical to human. They administered a gene therapy vector carrying cyclin A2 a week after heart attack to the experimental group and a null vector to the control group.

The study shows that the group treated with cyclin A2 demonstrated significant 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.

Additionally, mechanistic studies 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 of Icahn School of Medicine at Mount Sinai.

For this research study. Dr. Chaudhry led a multi-disciplinary team of physicians and scientists including the study’s co-first authors Drs. Scott Shapiro and Amaresh Ranjan of Icahn School of Medicine at Mount Sinai.

Dr. Chaudhry is a named inventor on patents relating to methods to prevent heart degeneration. Dr. Chaudhry also serves as an uncompensated officer on the Board of Directors and owns equity in VentriNova.

About VN-100

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, a gene that tells embryonic heart cells to divide and grow which is normally silenced in mammalian hearts after birth. Because this 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 IND-enabling studies have been initiated, and this publication marks the fifth scientific publication supporting the potential of this approach.

Source

Cyclin A2 Induces Cardiac Regeneration After Myocardial Infarction Through Cytokinesis of Adult Cardiomyocytes, Authors: Scott D. Shapiro, Amaresh K. Ranjan, Yoshiaki Kawase, Richard K. Cheng, Rina J. Kara, Romit Bhattacharya, Gabriela Guzman-Martinez, Javier Sanz, Mario J. Garcia and Hina W. Chaudhry, Sci. Transl. Med. (February 2014) DOI: 10.1126/scitranslmed.3007668

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