AC5 Inhibitor for Obesity

AC5 肥胖抑制剂

基本信息

批准号：
7807877
负责人：
Dorothy Eileen Vatner
金额：
$ 13.38万
依托单位：
VASADE BIOSCIENCES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-08-10 至 2012-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7807877
关键词：
Adenine Adverse effects Affect Age Amides Area Award Behavioral Genetics Blood - brain barrier anatomy Blood Glucose Blood specimen Body Weight Body Weight decreased Body fat Businesses Caloric Restriction Cardiac Cardiovascular system Catecholamines Chronic Clinical Collaborations Complement component C1s Country Data Data Analyses Development Diabetes Mellitus Diet Disease Dose Dreams Drug Formulations Eating Epidemic Exercise Exercise Tolerance Exhibits FDA approved Fatty acid glycerol esters Funding Generations Genes Genetically Engineered Mouse Goals Grant Health Health Benefit Heart failure Herpesviridae Institution Insulin Insulin Resistance Knock-out Lead Leptin Life Life Expectancy Link Longevity Marketing Measures Modeling Mus Nervous system structure New Jersey Obesity Patients Peripheral Nervous System Diseases Permeability Pharmaceutical Chemistry Pharmaceutical Preparations Pharmacologic Substance Phase Pilot Projects Population Private Sector Protein Isoforms Proteins Public Health Reporting Research Resistance Role Running Sales Serum Somatotropin Stress Suggestion Surface Technology Testing Therapeutic Time Toxic effect United States National Institutes of Health Weight Weight Gain Weight maintenance regimen Wild Type Mouse Work Xenical adenylyl cyclase type V cardiovascular risk factor commercialization feeding glucose tolerance immunosuppressed improved indexing inhibitor/antagonist innovation interest medical schools mouse model novel novel strategies novel therapeutic intervention orlistat phase 2 study pressure prevent public health relevance success validation studies

项目摘要

DESCRIPTION (provided by applicant): The goal of this proposal is to develop a drug that will be therapeutic for obesity and diabetes and improve exercise tolerance. Obesity, diabetes and exercise are inextricably linked such that an agent that improves exercise tolerance or prevents obesity or the development of diabetes will likely have a therapeutic role in all three conditions. Obesity is a global epidemic, which promotes diabetes and is a major cardiovascular risk factor, resulting in reduced life expectancy. Obesity and diabetes can be caused by dietary, behavioral and genetic factors. Both diseases are a public health problem and finding a novel therapeutic approach would be a major advance. Recently, we reported a novel, genetically engineered mouse model, where the adenylyl cyclase (AC) type 5 isoform is knocked out (AC5 KO). AC5 inactivation resulted in increased longevity and was protective against stress. Furthermore, the AC5 KO mice ate more than WT mice, but weighed less, suggesting that AC5 inhibition could be a novel approach to weight loss. The AC5 KO mouse also demonstrates enhanced exercise tolerance. Concurrently, we have developed a pharmacological AC5 inhibitor which also protects against cardiovascular stress. The main hypothesis of this pilot project is that inhibition of AC5 in mice protects against obesity. Our three working hypotheses are: A. Inhibition of AC5 will reduce obesity in mice fed a high fat diet, and B. Inhibition of AC5 will protect against the development of insulin resistance and diabetes, and C. Inhibition of AC5 will improve exercise tolerance in those mice. In view of the significance of obesity and diabetes in the US population, there is a major health benefit to this project. PUBLIC HEALTH RELEVANCE: Obesity is a global epidemic, which promotes diabetes and is a major cardiovascular risk factor, resulting in reduced life expectancy. Obesity and diabetes can be caused by dietary, behavioral and genetic factors; several genes have been identified to be involved in the development of obesity. Both diseases are a public health problem and finding a novel therapeutic approach would be a major advance.

描述（由申请人提供）：该提案的目的是开发一种对肥胖和糖尿病治疗的药物，并提高运动耐受性。肥胖，糖尿病和运动是密不可分的，使得能够提高运动耐受性或防止肥胖或糖尿病的发展的药物在所有三种疾病中都可能具有治疗作用。肥胖是一种全球流行病，可促进糖尿病，是主要的心血管危险因素，导致预期寿命降低。肥胖和糖尿病可能是由饮食，行为和遗传因素引起的。两种疾病都是一个公共卫生问题，找到一种新型的治疗方法将是一个重大进展。最近，我们报道了一种新型的基因工程小鼠模型，其中将腺苷环酶（AC）5同工型拆除（AC5 KO）。 AC5灭活导致寿命增加，并且可以防止压力。此外，AC5 KO小鼠的饮食量超过WT小鼠，但称重少，表明AC5抑制可能是一种新颖的减肥方法。 AC5 KO小鼠还表现出增强的运动耐受性。同时，我们开发了一种药理学AC5抑制剂，该抑制剂也可以防止心血管应激。该试点项目的主要假设是，在小鼠中抑制AC5可预防肥胖症。我们的三个工作假设是：A。抑制AC5将降低喂养高脂肪饮食的小鼠的肥胖症，并且B.抑制AC5将预防胰岛素抵抗和糖尿病的发展，C。对AC5的抑制作用将改善这些小鼠的运动耐受性。鉴于肥胖症和糖尿病在美国人口的重要性，该项目具有重大健康益处。公共卫生相关性：肥胖是一种全球流行病，可促进糖尿病，是主要的心血管危险因素，导致预期寿命降低。肥胖和糖尿病可能是由饮食，行为和遗传因素引起的。已经确定了几种基因参与肥胖的发展。两种疾病都是一个公共卫生问题，找到一种新型的治疗方法将是一个重大进步。