The Journal of Clinical Investigation Insight publishes preclinical results of urocortin 2 gene transfer in mouse models of insulin resistance
September 22, 2016
A one-time intravenous injection of an AAV8 vector encoding urocortin 2 provides long-term resolution of abnormal glucose disposal, suggesting a potential long-term therapy for clinical type 2 diabetes
San Diego, CA – Renova™ Therapeutics, a biotechnology company developing gene therapy and peptide infusion treatments for cardiovascular and metabolic diseases, announced its co-founder’s publication of preclinical research results of urocortin 2 gene transfer for the treatment of insulin resistance, an abnormality seen in clinical type 2 diabetes, in JCI Insight. The data indicate that gene transfer, via a one-time intravenous injection of a viral vector encoding urocortin 2, increases insulin sensitivity and glucose disposal, provides long-lasting resolution of abnormal glucose homeostasis, and reduces fatty infiltration of the liver in two mouse models of insulin resistance, suggesting a potential long-term therapy for clinical type 2 diabetes.
The preclinical studies were led by Dr. H. Kirk Hammond, Professor of Medicine at the University of California – San Diego and cardiologist at the Veterans Affairs San Diego Healthcare System, and his colleagues. Dr. Hammond is a co-founder of Renova Therapeutics and a consultant to the company.
In the preclinical studies, the urocortin 2 gene was administered intravenously via an adeno-associated virus (AAV) delivered predominantly to the liver. The approach resulted in normal blood glucose levels within weeks, which persisted for the three-month duration of the study. This proprietary approach exploits the use of peptide genes that possess favorable cardiometabolic effects via their paracrine activity.
Urocortin 2 gene transfer possesses advantages over current diabetes medications: It is insulin-sensitizing, circumvents the need for daily insulin injections, and reduces weight gain and fatty infiltration of the liver. These findings indicate a promising strategy for treating clinical type 2 diabetes and unlock the potential for treatment of other cardiovascular and metabolic diseases, including nonalcoholic fatty liver disease (nonalcoholic steatohepatitis – NASH).
Clinical type 2 diabetes, in which insulin resistance is seen, 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 1980.1 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.
“These preclinical results with urocortin 2 gene transfer are astonishing,” says Jack W. Reich, Ph.D., CEO and Co-founder of Renova Therapeutics. “We look forward to advancing this novel approach to treat one of the most prevalent chronic diseases in the world.”
Renova Therapeutics is planning to submit an Investigational New Drug application with the U.S. Food and Drug Administration in which patients with type 2 diabetes are enrolled to receive urocortin 2 gene transfer in well-controlled and safely conducted clinical trials. Urocortin 2 gene transfer in diabetes will be developed as an investigational gene therapy product known as RT-200.
1Worldwide 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.
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