Developing a Nutraceutical Product against Noise-Induce Hearing Loss

开发针对噪音引起的听力损失的营养保健产品

基本信息

批准号：
9459236
负责人：
Jianxin Bao
金额：
$ 22.47万
依托单位：
GATEWAY BIOTECHNOLOGY, INC.
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-21 至 2018-09-20
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9459236
关键词：
AIDS/HIV problem Address Affect American Anatomy Animals Anti-Inflammatory Agents Anti-inflammatory Antiepileptic Agents Antioxidants Auditory Brainstem Responses Calcium Channel Calcium Signaling Chinese Herbs Clinical Clinical Research Cochlea Complex Country Data Development Dose Drug Combinations Environment Environmental Hazards Exhibits Free Radicals Funding Future Goals Harvest Hearing Herb Histopathology Hour Human Industrialization Inflammatory Institutional Review Boards Integrative Medicine Intervention Magic Malignant Neoplasms Market Research Measurement Measures Modeling Molecular Molecular Target Mus Noise Noise-Induced Hearing Loss Nutraceutical Occupational Outcome Study Pathway interactions Patients Pharmaceutical Preparations Pharmacodynamics Pharmacology Phase Presbycusis Prevention Program Development Property Rattus Recording of previous events Safety Signal Pathway Signal Transduction Small Business Innovation Research Grant Stephania tetrandra Testing Therapeutic United States Visit Work base cellular targeting clinical application dosage effective intervention effective therapy experience experimental study feeding hearing impairment innovation occupational hazard phase 2 study pre-clinical pressure prevent programs prophylactic research and development sound therapeutic target

项目摘要

PROJECT SUMMARY The most common occupational and environmental hazard in this country is noise. It's not surprising, then, that noise-induced hearing loss (NIHL) is the second most common form of sensorineural hearing deficit, behind only age-related hearing loss (presbycusis). Although therapeutics that target the free radical pathway have shown promise for reducing NIHL, there are no effective nutraceuticals or approved medications for NIHL. Development of an efficacious treatment has been hampered by the complex array of cellular and molecular pathways involved in NIHL. Our preliminary studies have shown that the Chinese herb Stephania tetrandra and its main extract, tetrandrine (TET), can effectively protect against NIHL in mice. Clinical use of this herb has exhibited an excellent long-term safety profile. Moreover, TET possesses strong antioxidant and anti-inflammatory properties, and can also block calcium channels, thus targeting three main signaling pathways that underlie NIHL. Consistent with the funding priorities at National Center for Complementary and Integrative Health, in this Phase I application, we will determine the median effective dose (ED50) for this herb extract to prevent (Aim 1) and treat (Aim 2) NIHL in rats using a long noise exposure model (8 hours per day) similar to most industrial working environments. The innovative aspects of our approach are: (1) developing a nutraceutical against NIHL, thus breaking a major access barrier for customers, who are more likely to visit audiologists for hearing treatment; (2) testing in a rat model with cumulative noise exposure similar to that encountered by factory workers; (3) selecting an herb with well-characterized pharmacological properties and a long safety history of clinical applications; and (4) targeting multiple signaling pathways that underlie NIHL. If the outcome of this study is successful, we will then obtain institutional review board (IRB) approval to conduct SBIR Phase II studies in humans of this nutraceutical against NIHL. The goal of our program is to bring this nutraceutical to market for use in the prevention and treatment of NIHL. If this approach is successful, similar nutraceuticals will be evaluated for potential prevention of presbycusis.

项目概要这个国家最常见的职业和环境危害是噪音。它是因此，噪声性听力损失 (NIHL) 是第二常见的听力损失也就不足为奇了一种感音神经性听力缺陷，仅次于年龄相关性听力损失（老年性耳聋）。尽管针对自由基途径的治疗已表明承诺减少 NIHL，但尚无有效的营养保健品或已获批准 NIHL 药物。有效治疗方法的开发受到以下因素的阻碍 NIHL 涉及的一系列复杂的细胞和分子途径。我们的初步研究表明，中药防己及其主要提取物，粉防己碱 (TET) 可以有效预防小鼠 NIHL。这种草药的临床用途表现出出色的长期安全性。此外，TET还拥有强大的抗氧化和抗炎特性，还可以阻断钙通道，从而针对 NIHL 基础的三个主要信号通路。与资金一致国家补充和综合健康中心第一阶段的优先事项应用中，我们将确定该草药提取物的中位有效剂量 (ED50) 使用长期噪声暴露模型预防（目标 1）和治疗（目标 2）大鼠 NIHL（8 每天小时）类似于大多数工业工作环境。创新方面我们的方法是：(1) 开发一种针对 NIHL 的营养保健品，从而打破一个重大的客户的访问障碍，他们更有可能拜访听力学家进行听力检查治疗; (2) 在累积噪声暴露相似的大鼠模型中进行测试工厂工人遇到的； (3)选择性状好的药材药理特性和长期的临床应用安全历史；和（4）针对 NIHL 背后的多个信号通路。如果这项研究的结果是如果成功，我们将获得机构审查委员会 (IRB) 的批准来进行 SBIR 这种营养保健品针对 NIHL 的人体 II 期研究。我们计划的目标旨在将这种营养保健品推向市场，用于预防和治疗 NIHL。如果这种方法是成功的，将评估类似的营养保健品的潜力预防老年性耳聋。