Evaluation of ACT1 to Treat Diabetic Keratopathy

An estimated 29.1 million people in the United States have diabetes, and its prevalence is rising. Diabetes is a leading cause of blindness and vision problems. Diabetic keratopathy, which occurs in about half to two-thirds of people with diabetes, is a condition that produces chronic injury and damage to the cornea, the clear outer part of the eye. This project will involve further development and safety studies of ACT1, a potential therapeutic compound for diabetic keratopathy. ACT1 enhances wound healing by blocking the action of a protein that promotes injury signals. In addition to diabetic keratopathy, ACT1 could be used to treat cornea injuries due to military activities or eye surgery. This project will prepare ACT1 for testing in humans.

Scientific Synopsis

Diabetes is a leading cause of blindness and visual impairments. Diabetic keratopathy, characterized by corneal thinning, disorganization, and persistent epithelial defects, is recognized as a significant cause of morbidity associated with the disease, presenting in an estimated 47-64% of diabetics. Unlike in normoglycemic individuals, diabetic corneal defects are associated with abnormal corneal re-epithelialization and individuals with diabetes present with persistent corneal wounds that are unresponsive to conventional treatment regimens.

FirstString Research is a clinical stage biotech company with clinical success in developing therapeutic peptides for applications in tissue engineering and regenerative medicine.  FirstString’s lead peptide, ACT1, is based on the C-terminal sequence of connexin43 (Cx43) and is designed to enter the cell and competitively inhibit the binding of endogenous Cx43. Cx43 plays critical roles in multiple aspects of wound healing, including spread of injury signals, extravasation of immune cells, granulation tissue formation, and fibrosis. A topical gel formulation of ACT1 (Granexin) is in Phase III clinical development for chronic wound healing and scar reduction.

Studies in preclinical models of efficacy show significant enhancement in corneal re-epithelialization and wound closure following ethanol-induced corneal burn injuries in diabetic rats, as compared with controls. Given the success of ACT1 in dermal indication programs and the positive preclinical efficacy outcomes in relation to corneal healing, the objectives of this BrIDGs application are aimed at safety evaluation and optimization of an ACT1 formulation with the goal to complete a preclinical safety package for an Investigational New Drug (IND) application and pave the way for human clinical evaluation.

In addition to addressing the medical needs of an expanding diabetic population, this formulation may be applicable in corneal injuries resulting from military engagement or corneal epithelial damage obtained during cataract or corneal refractive surgery.

Lead Collaborator

FirstString Research, Inc., Mount Pleasant, South Carolina
Gautam Ghatnekar, Ph.D.

Public Health Impact

Reports from the American Diabetes Association indicate that an estimated 29.1million people in the US have diabetes. The chronic nature of diabetes, severity of its complications, and the disease management resources puts an enormous economic and societal burden on the individual, family, and healthcare system.


BrIDGs program scientists are collaborating on completion of formulation development, and pharmacokinetic and IND-directed toxicology studies.