Pre-Clinical Development of Topical Pirenzepine for Treating Diabetic Neuropathy

DESCRIPTION provided by applicant The objective of this SBIR fast track project is to expediently advance pre clinical development of a new therapeutic for diabetic neuropathy Of the million Americans who suffer from diabetes approximately will be diagnosed with neuropathy which is characterized by nerve degeneration Despite the high prevalence of the disease there is currently no FDA approved treatment to either prevent diabetes induced nerve degeneration or promote nerve regeneration Thus there is a substantial unmet need to develop more effective treatments for diabetic neuropathy The founders of WinSanTor have identified a promising candidate which both prevents and reverses neuropathy in rodent models of the disease The candidate molecule pirenzepine was identified using a novel screening methodology developed in the labs of the companyandapos s founders Pirenzepine has subsequently been evaluated in over a dozen in vivo tests and has demonstrated the unique ability to ameliorate both epidermal fiber loss and thermal hypoalgesia Pirenzepine is an approved drug for other indications in non US countries and so it is substantially de risked as a drug development candidate Based on the moleculeandapos s significant potential as a first in class molecule for treating diabetic neuropathy we propose a fast track project to rapidly advance pre clinical development of the molecule Phase I Specific Aims are Assess in vitro release and retention single dose pharmacokinetics and tissue distribution of topically administered pirenzepine Determine acute toxicity under non GLP conditions Evaluate genotoxicity and hERG under non GLP conditions Conduct dermal toxicity studies under non GLP conditions The metrics of success to advance to Phase II are Identification of at least one formulation in which sufficient quantities of active ingredient are present in the tissues and plasma following topical administration porcine model and No significant toxicity liabilities Phase II Specific Aims are Develop analytical techniques and obtain GMP material Conduct acute toxicity and month toxicity studies with two animal species under GLP conditions Conduct safety toxicology and genotoxicity studies under GLP conditions Conduct dermal toxicity studies under GLP conditions The metric of success of Phase II is to develop a complete safety package that will be submitted to the FDA as part of an IND filing PUBLIC HEALTH RELEVANCE There is currently no FDA approved treatment to either prevent diabetes induced nerve degeneration or promote nerve regeneration and so there is an urgent need for therapies that can provide relief for this painful and debilitating condition The founders of WinSanTor have identified a known compound pirenzepine which effectively prevents and reverses nerve degeneration in rodent models of diabetes through a previously unexplored mechanism of action This project will accelerate pre clinical development of pirenzepine as a novel therapeutic for diabetic neuropathy