A New Treatment for A Diabetic Eye Disease?

By Jane Farrell

Researchers have identified a compound that can help reduce diabetic retinopathy, an eye disease affecting one third of the estimated 30 million Americans who have diabetes.

Diabetic retinopathy, in which a patient’s vision slowly fades, is irreversible. Few treatments are available.

The finding, published in the Oct. 23, 2017 issue of The Journal of Clinical Investigation, represents an opportunity to develop new treatments for diabetic retinopathy.

“What is exciting about this study is that we and our collaborators identified a compound [NAV-2729] that inhibits [the protein] ARF6, which is crucial for the development of diabetic retinopathy,” explained co-first author Weiquan (Wendy) Zhu, Ph.D., research assistant professor in Internal Medicine at University of Utah Health.

Studies were conducted in rodents treated to simulate the diabetic condition. By injecting NAV-2729 into the eyes of these animals, vessel leakage, as well as, the overgrowth of blood vessels, another driver of disease, were significantly reduced.

The long-term efficacy of treatment remains unknown. It also remains to be determined whether the drug will be suitable as a therapeutic intervention for people.

“ARF6 acts like a traffic cop at a busy intersection within a cell,” explained Dean Li, Ph.D., vice president, Head of Translational Medicine at Merck & Co. and senior author on the paper. Li is the former associate vice president and chief scientific officer at U of U Health and co-founder of Navigen Inc. “ARF6 orchestrates multiple inflammatory signals that contribute to inflammation common in many diseases, including diabetic eye disease.”

ARF6 amplifies and maintains the signal protein (vascular endothelial growth factor (VEGF)) receptor, which stimulates a series of cascading responses, leading to a diseased state in the eye.

Today, patients with diabetic eye disease can receive monthly anti-VEGF injections directly into the eye to reduce inflammation, a treatment that is successful in only 40 percent of patients. In the study, injections of NAV-2729 into the eyes of diabetic mice were more effective in reducing blood vessel leakage than the anti-VEGF injections.

“Diabetic retinopathy can develop over time, leading to dramatic vision loss that may not be improved with glasses,” said M. Elizabeth Hartnett, M.D., professor in Ophthalmology and Visual Sciences at Moran Eye Center and a contributor to this study. “New treatments are needed, because diabetic retinopathy is increasing world-wide and anticipated to increase more in the next decades.”

The team of researchers plan to continue to explore the role of ARF6 in other inflammatory diseases.

NAV-2729 was identified by A6, a subsidiary company of Navigen Inc, a Salt Lake City drug discovery and development company, whose research scientists contributed to this study.