DESCRIPTION (provided by applicant): According to the American Diabetes Association, there are more than 16 million people in the United States with known diabetes. Diabetic patients commonly demonstrate impaired wound healing. Approximately 20 percent of patients with diabetes will develop foot ulceration in their lifetime. Diabetic foot ulceration (DFU) represents a major problem that can significantly impair the patient's quality of life, require prolonged hospitalization, and may involve infection, gangrene, and amputation. It has been estimated that for each new foot ulcer the attributable cost for a middle-aged diabetic man in the first two years is approximately $ 30,000. The cost of DFU to the healthcare system is over one billion dollars per year in the United States. A well- established reason as to why diabetic wounds are tough to heal is that they do not progress through the normal healing phases. Instead, it is thought that diabetic wounds are caught and remain trapped in the initial inflammatory phase of wound healing. FirstString Research, Inc. (FSR) is a biotech company located in Charleston, South Carolina. The founders of FSR, Drs. Robert Gourdie and Gautam Ghatnekar are co inventors of a class of novel bioengineered peptides - we refer to as ACT peptides. Phase I funded studies in the diabetic C57BL/KsJ-m+/+Leptdb (db+/db+) mouse model have provided strong evidence for efficacy and potential of the ACT1 peptide in the treatment of diabetic wounds. The peptide effects a significantly faster closure rate. Subjective parameters such as redness and overall appearance were also substantially improved in ACT1 treated wounds. ACT1 peptide did not show any adverse reactions or safety concerns in our Phase I SBIR studies, as evaluated by a complete necropsy and histopathological evaluation. Moreover, to enhance our ability to understand and anticipate issues associated with the safety and efficacy of ACT1peptide, we will also use gene microarray and computational approaches to analyze effects on key signaling pathways involved in wound healing. Of particular interest will be changes induced in angiogenic signaling that provide basic mechanistic insight into the regeneration of skin vascular pattern in wounds treated with ACT1 peptide. Our market research has indicated that present therapies and drugs for wound healing in diabetes and chronic wounds in general are predominantly symptomatic, empirical, unpredictable, and largely ineffective. Our ACT1 peptide potentially offers a mechanistically based solution to not just faster wound closure but also significant cost savings and more importantly improving the quality of life in diabetic patients. In this Phase II application, Dr. Paul Ehrlich, Director for the Wound Healing Research Laboratory in the Division of Plastic Surgery, Department of Surgery, Hershey Medical Center at Penn State University and Dr. Indu Parikh, President and CSO, BioMarck Pharmaceuticals, Durham, NC have agreed to assist us in achieving our aims. PUBLIC HEALTH RELEVANCE: Diabetes is a debilitating condition that threatens the quality of life of not just the people suffering from the disease but also family members and loved ones. Approximately 20 percent of patients with diabetes develop foot ulceration in their lifetime and they demonstrate impaired wound healing. A well-accepted reason for the poor healing of the diabetic or chronic wounds in general is that they are 'stuck' in the inflammatory phase. This technology provides promise for reduced inflammation and faster healing of diabetic wounds thereby improving the quality of life and saving millions of dollars in health care related costs.

Project Narrative: Diabetes is a debilitating condition that threatens the quality of life of not just the people suffering from the disease but also family members and loved ones. Approximately 20 percent of patients with diabetes develop foot ulceration in their lifetime and they demonstrate impaired wound healing. A well-accepted reason for the poor healing of the diabetic or chronic wounds in general is that they are 'stuck' in the inflammatory phase. This technology provides promise for reduced inflammation and faster healing of diabetic wounds thereby improving the quality of life and saving millions of dollars in health care related costs.