Determining Effectiveness of V-10 Self-Assembling Pro-Angiogenic Peptide in Re-Vascularizing and Accelerating Wound-Healing in a BBZDR Rat Model of Diabetic Foot Ulceration

Project Summary / Abstract NangioTx has developed a patented technology for promoting neovascularization in ischemic tissues. Its lead compound is a 33-amino-acid pro-angiogenic peptide V-10, which, when injected into an ischemic tissue microenvironment, generates mature microvasculature, aiding tissue regeneration. A proof of concept for such tissue regeneration has been obtained in a murine hind-limb ischemia model. The FDA has informed us that this proof of concept is sufficient for NangioTx to test the compound in humans provided that we document that no toxic or undesirable side effects are associated with our peptide. The company is now conducting formal safety and toxicity studies to support a future IND application. We have selected Diabetic Foot Ulcers (DFU) as our initial therapeutic target. DFU is a serious complication in andgt;23 million diabetics in the U.S., doubling the cost of care per patient. Each diabetic is likely to develop at least one diabetic ulcer during the course of the disease. Lesions of this type can enlarge quickly, become infected and require radical clinical intervention including limb amputation. Conventional management of DFU involves frequent visits to physician offices while the more advanced/expensive treatments are not generally effective, leaving the patient to endure a chronic health condition. The processes associated with the development of DFU involve dysfunction in many elements of normal wound healing mechanisms, such as the poor production of blood-vessel networks needed for wound resolution. We hypothesize that our pro-angiogenic peptide scaffold will initiate development of new mature blood vessels in the DFU tissue, facilitating wound healing could proceed. In this SBIR grant application, we aim to determine the efficacy of this material to generate new blood vessels in a established and validated diabetic rat model of chronic, slow-healing wounds. A total of 40 inbred Bio-Breeding Zucker diabetic rats will be randomized into five experimental groups each comprised of 8 animals. Wounds will be treated by the application of V-10 hydrogel or vehicle as follows: Group A will receive a topical application of 25 µL V-10; Group B will be treated with an equal volume of vehicle; Group C will receive 25 µL of V-10 hydrogel by intramuscular injection; Group D will receive 50 µL V-10 hydrogel by intramuscular injection; and Group E will serve as the vehicle control for the injected groups. Tissue samples collected from the animals after 30 days of treatment will be examined by histopathology for parameters of inflammation, granulation, and re- epithelialization. Fibrous connective tissue in the granulation bed will be quantified using a computerized image- analysis system. In parallel, storage stability of V-10 and its formulation will be monitored throughout the duration of the study using mass spectrometry. Any detected degradation product at level of andgt;1% will be characterized. Success in this project would increase the confidence of potential investors in NangioTx regenerative technology; it would accelerate our preclinical and translational efforts by attracting funding to complete studies necessary for a successful IND application, thus enabling our company to develop a new therapy that would fill a significant unmet medical need in DFU.Project Narrative There are no effective drugs available to treat diabetic foot ulceration (DFU) – chronic non-healing wounds - afflicting an increasing number of diabetic and obese patients. The wounds do not heal because microvasculature – small blood vessels of the wound - have been damaged by the disease. Our company has developed a drug that makes new blood vessels, and we will examine using a rat model of chronic, slow-healing wounds whether making new blood vessels helps to heal diabetic ulcers.