权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Pre-Clinical Development of Topical Pirenzepine for Treating Diabetic Neuropathy

局部哌仑西平治疗糖尿病神经病变的临床前开发

基本信息

批准号：
9097695
负责人：
Angela Hansen
金额：
$ 59.17万
依托单位：
WINSANTOR, INC.
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-30 至 2017-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9097695
关键词：
American Animals Biological Assay Canis familiaris Cardiovascular system Cavia Cells Clinical Trials Country Cutaneous Data Dermal Development Diabetes Mellitus Diabetic Neuropathies Diabetic mouse Diagnosis Diffusion Disease Dose Drug Kinetics Drug or chemical Tissue Distribution Evaluation FDA approved Family suidae Fiber Formulation Funding Goals Health High Prevalence In Vitro Insulin-Dependent Diabetes Mellitus Maximum Tolerated Dose Measures Methodology Methods Micronucleus Tests Miniature Swine Modeling Nerve Degeneration Nerve Regeneration Neuropathy Non-Insulin-Dependent Diabetes Mellitus Oral Oryctolagus cuniculus Pain Participant Patients Pharmaceutical Preparations Pharmacology Phase Phototoxicity Pirenzepine Plasma Public Health Radiolabeled Rattus Risk Rodent Model Safety Small Business Innovation Research Grant Streptozocin Techniques Telemetry Testing Therapeutic Tissues Topical application Toxic effect Toxicology United States National Institutes of Health Work acute toxicity base drug development effective therapy genotoxicity in vivo irritation mouse model novel novel therapeutics pre-clinical preclinical study prevent programs radiotracer respiratory screening success

项目摘要

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 25 million Americans who suffer from diabetes, approximately 50% 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 company'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 molecule'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: 1) Assess in vitro release and retention, single dose pharmacokinetics, and tissue distribution of topically administered pirenzepine. 2) Determine acute toxicity under non-GLP conditions. 3) Evaluate genotoxicity and hERG under non-GLP conditions. 4) Conduct dermal toxicity studies under non-GLP conditions. The metrics of success to advance to Phase II are: 1) 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 2) No significant toxicity liabilities Phase II Specific Aims are: 1) Develop analytical techniques and obtain GMP material. 2) Conduct acute toxicity and 3-month toxicity studies with two animal species under GLP conditions. 3) Conduct safety toxicology and genotoxicity studies under GLP conditions. 4) 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.