According to the World Health Organization, at least 171 million people worldwide are living with diabetes and this figure is likely to more than double by the year 2030. Because of its chronic nature, the severity of its complications and the means required to control them, the economic burden is enormous not only to the individuals and families involved but also to the health system. Wound healing in diabetics, in general, is severely impaired, which has a great impact on the economic and social burden of our society. Diabetes is the leading cause of new cases of blindness among adults aged 20-74 years. Although retinopathy is the primary cause of blindness in these patients, in the past 3 decades it has been noted that 47-64% of diabetic patients will manifest diabetic keratopathy or other corneal abnormalities, which are potentially sight threatening. Currently, therapies to treat these corneal epithelial wounds are very limited. FirstString Research, Inc is an early stage biotech company developing therapeutic peptides for applications in tissue engineering and regenerative medicine. FirstString's lead novel bioengineered peptide dubbed ACT1, is based on the C-terminal sequence of connexin 43 (Cx43), and shows great promise in modulating intercellular communication. ACT1 works by stabilizing gap junctions and maintaining intercellular communication between cells that is essential for wound repair or injury response. Preliminary data from our company has indicated that this peptide can effect accelerated wound healing, reduce inflammatory response, reduce scar formation and restore skin structure following acute injury in a diabetic mouse model system. Furthermore, ACT1 peptide has been shown to promote corneal wound closure following ethanol burn injuries to the rat cornea, compared with that of a control peptide. Based on these early findings we hypothesize that ACT1 peptide will increase corneal re-epithelialization and accelerate wound closure following injury to the corneas of diabetic rats as demonstrated by the aims outlined in this Phase I SBIR application. The completion of aims outlined in this project will set the stage for a future Phase II SBIR and could lead to a commercially viable therapeutic in the clinical management of diabetic keratopathy.

Public Health Relevance

According to the World Health Organization, at least 171 million people worldwide are living with diabetes. Corneal disorders secondary to diabetes, such as diabetic keratopathy, are an increasing cause of morbidity associated with diabetes and affects 47-64% of diabetics during the course of their disease. Conventional therapies for the treatment of these corneal wounds have failed. FirstString Research Inc. has developed a novel therapeutic peptide that may promote re-epithelialization of the cornea, reduce scarring and inflammation and thereby prevent potential blindness in diabetics with such disorders.

National Institute of Health (NIH)
National Eye Institute (NEI)
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
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Special Emphasis Panel (ZRG1-IMST-K (11))
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Wujek, Jerome R
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Firststring Research, LLC
MT. Pleasant
United States
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Grek, Christina L; Rhett, J Matthew; Ghatnekar, Gautam S (2014) Cardiac to cancer: connecting connexins to clinical opportunity. FEBS Lett 588:1349-64