This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Diabetic peripheral neuropathy trials have largely relied on the same measurements to determine whether an investigational drug may provide a benefit. These measures include nerve conduction velocity testing and quantitative sensory testing and were historically developed as tools to diagnose peripheral neuropathy as opposed to measuring a drug effect. These measures, while excellent for their intended purpose of diagnosis do not appear to be sensitive to small changes in nerve function as may occur in the setting of a clinical trial. As a result, there is a sense that some trials may have failed not because the drug did not provide a benefit, but rather that investigators were not able to detect those improvements. The nerves in the skin can be reliably measured using punch skin biopsies and are very relevant to diabetes. There is strong evidence that they are often the earliest sign of neuropathy. Furthermore, the biopsy technique gives a direct measure of nerve integrity while other clinical tests extrapolate this information indirectly. Finally, nerves in the skin are easily accessible and by extension can be injured in a standardized, safe and relatively innocuous fashion. This allows the rate of nerve recovery or regeneration to be precisely determined. The purpose of this clinical trial is to determine whether the investigational compound FK1706, is able to accelerate the rate of epidermal nerve fiber regeneration using validated cutaneous nerve injury models. Epidermal innervation is particularly relevant to FK1706 as preclinical studies indicate that the mechanism of action of FK1706 is directed at potentiating the effect of endogenous nerve growth factor (NGF). Cutaneous nerve fibers are among the class of nerve fibers that is responsive to NGF, while large myelinated nerve fibers (those that are primarily tested in nerve conduction velocity and quantitative sensory testing) are unresponsive to NGF's effects.This mutlicenter regenerative diabetic neuropathy study is coordinated through Johns Hopkins and uses models of cutaneous nerve regeneration that have been developed over the past 5 years.
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