Multivalent Conjugates of Sonic Hedgehog to Accelerate Diabetic Wound Healing

DESCRIPTION In nearly one million Americans with diabetes were diagnosed with a lower extremity ulcer and failure of these wounds to heal resulted in more than lower extremity amputations Valitor Inc is developing protein polymer therapeutics to overcome the micro vascular consequences of diabetic wound healing We designed our therapy to complement the standard practice of diabetic ulcer management and to reduce the costly serial effort required for debridement and clinical observation of these slowly healing wounds Our patented technology is a bio conjugation process that enables us tether Sonic hedgehog Shh an important angiogenic factor to linear chains of hyaluronic acid HyA at defined Shh HyA ratios i e valency In Phase I of this project we verified that Shh valency correlated with enhanced Shh induced cellular functions including downstream angiogenic signaling which were substantially unregulated relative to equimolar concentrations of unconjugated Shh We further demonstrated that after treatment with multivalent Shh conjugates mvShh full thickness excisional wounds in db db diabetic mice exhibited significantly greater neovascular density and faster closure times compared to wounds treated with unconjugated Shh or vehicle controls Our overall goal during Phase II is to build on these promising proof of mechanism results by completing the lead optimization process and to advance mvShh to as a candidate for pre clinical studies PUBLIC HEALTH RELEVANCE In nearly one million Americans with diabetes were diagnosed with a chronic lower extremity ulcer and these patients generate over $ billion per year in related health care costs Valitor Inc is developing an advanced therapeutic to accelerate healing in diabetic wounds offsetting the high cost of treatment by encouraging neovascularization and improving blood supply in the wound bed The overall goal of our Phase II project is to determine the molecular parameters of our therapy that generate the greatest therapeutic effect and to advance our technology toward clinical translation as a drug product