A therapy for improving diabetic ulcer healing

Diabetic ulcer is one of the major complications of diabetes mellitus because of poor management of hyperglycemia. The prevalence of diabetic ulcer ranges from 14 to 24% among diabetes patients. In the U.S., diabetic ulcer affects over 900,000 peoples a year, and leads to rt80,000 limb amputations annually. It was estimated that the management of diabetic ulcers represents over one third of the total cost of treatment of diabetes complications in developed countries. Current management of diabetic ulcers mainly focuses on the elimination of infection, the use of dressings to maintain a moist wound bed, offloading high pressure in the extremities, and debridement to improve healing. Although these measures have improved the survival of patients, there is a lack of pharmacotherapy that can substantially improve the healing of chronic wounds in diabetes patients. Clearly, novel therapeutics that can improve wound healing and prevent the recurrence of chronic ulcers in diabetes are much needed. Recent advance has shown that adrenomedullin family peptides play crucial roles in the regulation of vasculogenesis and immune response, and can protect against diabetes- associated etiology. These peptides have also been shown to accelerate wound healing, perhaps by improving angiogenesis, immune response, vascular permeability, and tissue regeneration in wound sites. Because these peptides have poor stability in vivo, they are poor drug candidates. To overcome this obstacle, we have developed a series of super-agonistic analogs that self-assemble to form gels in situ and slowly release the monomeric analog in vivo. Based on this discovery, we propose to develop an analog gel therapy for accelerating wound healing in diabetes patients by improving re-epithelialization, granulation, blood flow, and revascularization within the wound environment. In the proposed study, we will (1) identify an optimal gel formulation that provides sustained and localized treatment in vivo and (2) investigate the efficacy of the selected analog gel on wound healing in two rodent diabetic ulcer models. Successful development of this novel hormonal therapy has the potential to significantly reduce the mortality and morbidity resulting from nonhealing foot ulcers among diabetes patients.