JACC: Basic to Translational Science publishes article comparing effects of urocortin 2 versus urocortin 3 gene transfer on left ventricular function and glucose disposal
SAN DIEGO, Calif., May 4, 2018 — Renova™ Therapeutics, a biotechnology company developing gene and peptide-based treatments for cardiovascular and metabolic diseases, today announced its cofounder’s publication of an article in JACC: Basic to Translational Science 2018;3:249-64. The article is authored by Dimosthenis Giamouridis, Mei Hua Gao, N. Chin Lai, Zhen Tan, Young Chul Kim, Tracy Guo, Atsushi Miyanohara, W. Matthijis Blanksteijn, Erik Biessen and H. Kirk Hammond from Veterans Affairs San Diego Healthcare System, University of California San Diego, and Cardiovascular Research Institute Maastricht University, the Netherlands.
Many patients with diabetes have heart failure. The study from Dr. Hammond’s laboratory examined the effect of gene transfer using an adeno-associated virus vector (AAV8) carrying either urocortin 2 (UCn2) or urocortin 3 (UCn3) in normal mice. The effects of UCn2 and UCn3 on left ventricular (LV) systolic and diastolic function and glucose disposal were the focus of the study. Mechanistic studies included quantification of LV sarco/endoplasmic reticulum Ca2+ -ATPase (SERCA 2a) content, and cardiac myocyte calcium handling.
After intravenous delivery of the vector, UCn2 and UCn3 are expressed predominantly in the liver and released to the circulation where they activate corticotropin releasing hormone receptor-2 (CRHR2) in the heart, skeletal muscle and vasculature. Benefits include increased heart function and increased glucose disposal. This approach enables patients to be treated by a simple IV injection during an office visit. The method of gene transfer of genes encoding peptides with potential beneficial cardiovascular effects through their paracrine activity is a new concept. Renova Therapeutics holds a worldwide exclusive license to this intellectual property.
Data were obtained nine weeks after gene transfer, and showed that UCn2 and UCn3 gene transfer both increased LV systolic and diastolic heart function, but that only UCn2 reduced fasting blood glucose and increased glucose disposal. Increases in LV SERCA2a content and enhanced calcium handling in cardiac myocytes were seen with both UCn2 and UCn3 gene transfer. Previous studies from Dr. Hammond’s laboratory showed that UCn2 gene transfer increases the function of the failing heart and, in addition, restores insulin sensitivity in two models of insulin resistance. In addition to application in heart failure and diabetes these data indicate that UCn2 or UCn3 gene transfer by a single intravenous administration may result in prolonged improvement in diastolic heart function, and therefore may be useful for patients with heart failure and preserved ejection fraction (HFpEF). At present there are no treatments approved for HFpEF that reduce hospitalization rate and mortality.
About heart failure
Heart failure is a chronic disease characterized by the inability of the heart to pump sufficient blood to meet the body’s demands. It is a progressive and fatal chronic condition, and symptoms worsen over time. Heart failure afflicts more than 28 million people globally and is the only cardiovascular disease that is increasing in prevalence. In the United States, it is the most common cause for emergency hospital admissions in patients 65 and older.
About type 2 diabetes
Type 2 diabetes accounts for up to 95% of the world’s diabetes cases. It is associated with coronary artery disease, peripheral vascular disease and amputation, stroke, heart failure, kidney failure, blindness and peripheral neuropathy. Few diseases are as prevalent and affect so many organ systems as diabetes.
The discovery and development of more effective therapies for type 2 diabetes is imperative. The global prevalence of diabetes is estimated to be 422 million adults, a number that has nearly quadrupled from 108 million in 1980. In 2012, an estimated 1.5 million deaths were related to diabetes. The global annual cost of diabetes is USD 827 billion. In the United States, people with diabetes incur average medical expenditures of USD 13,700 per year, according to the American Diabetes Association.
About Renova Therapeutics
Renova Therapeutics is developing definitive, one-time gene therapies and peptide infusion treatments to restore the health of people suffering from chronic diseases. The first indications the company is pursuing are gene therapy treatments for heart failure and type 2 diabetes, two of the most common and devastating chronic diseases in the world. The company’s lead product candidate, RT-100, is a treatment that delivers a therapeutic gene directly to the heart during a routine outpatient procedure and has the potential to improve heart function in millions of patients with heart failure. The company’s product pipeline also includes a groundbreaking gene therapy in preclinical development for patients with type 2 diabetes, as well as a peptide infusion therapy for acute decompensated heart failure. Renova Therapeutics was founded in 2009 and is led by an experienced management team in biopharmaceuticals and gene therapy. For additional information about the company, please visit www.renovatherapeutics.com.
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- Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4.4 million participants. The Lancet, Volume 387, Issue 10027, 1513 – 1530.
President, Renova Therapeutics