Evaluating the Effect of a Local Microvascular Tissue Graft Treatment in Rat Models of Diabetic Peripheral Neuropathy

Microvascular Tissues, Inc., Jamaica Plain MA

Investigators

Abstract

PROJECT SUMMARY Diabetic peripheral neuropathy (DPN) is a progressive disease, and currently, there are no well-recognized effective treatments shown to be able to address DPN and improve or return sensation to extremities. MicroVascular Tissues, Inc. (MVT), has developed microvascular tissue graft (mVASC), a novel, human structural allograft consisting of lyophilized and terminally sterilized allogeneic microvascular tissue. mVASC’s primary function is to serve as a scaffold for cellular invasion and capillary growth, resulting in improved microcirculatory blood flow. The benefits of improved microcirculatory blood flow may be particularly impactful on patients with compromised microvasculature, such as patients with diabetes. At the microvascular level, the connection between capillary function and nerve function is well established, and improved blood flow could significantly impact the function of the impaired nerves present in peripheral neuropathy. This may serve to increase a patient’s quality of life on several fronts, such as improving sensation, decreasing neuropathic pain, increasing the ability to walk or exercise, reducing ulcerations and hospitalizations, and preserving limbs. mVASC has been studied in a Level 1, prospective, randomized, controlled, multicenter clinical trial with nonhealing Wagner 1-2 neuropathic foot ulcers (the “HIFLO Trial”). This trial demonstrated that the application of mVASC safely closed a significantly greater percentage of wounds than the standard-of-care group, and demonstrated an increased level of perfusion and tissue quality in the wound site in a sub-study of patients. Remarkably, HIFLO Trial patients receiving mVASC also demonstrated a statistically significant increase in sensation and a corresponding decrease in the neuropathic area during the treatment period. The improvement in neuropathy shown in the mVASC HIFLO trial, combined with success in improving sensation in several pilot case studies treating diabetic patients with DPN (without active ulcers) with a one-time mVASC injection, has led MVT to hypothesize that mVASC treatment may benefit neuropathic patients in general. Hence, we propose to use mVASC as an injectable treatment to determine whether it directly impacts mild to moderate neuropathy. Specifically, MVT proposes this Phase I SBIR project to support preclinical studies to better understand the preliminary results of mVASC’s effect on DPN and sensation utilizing rigorous and well-accepted research models and assessment tools. The outcome could have a significant health benefit for diabetic patient care, including durable improvement in peripheral neuropathy and sensation and reduced ulcer occurrence. MVT intends to apply for a Phase II SBIR grant to conduct a randomized, multi-center clinical trial with long-term follow-up in patients with DPN. This clinical study envisions evaluating the efficacy of mVASC in limiting the progression of neuropathy and improving sensation based on quantitative measurements and patient-reported outcomes, including changes in microvascular perfusion, sudomotor function and other neuropathy endpoints, and risk of ulceration.