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

• 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
• 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

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.

项目总结 在这个国家，最常见的职业和环境危害是噪音。它是 因此，噪音引起的听力损失(NIHL)是第二常见的也就不足为奇了 感音神经性听力障碍的形式，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方法已经表明 承诺减少NIHL，没有有效的营养食品或批准 治疗NIHL的药物。有效疗法的开发一直受到以下因素的阻碍 参与NIHL的细胞和分子通路的复杂阵列。我们的预赛 研究表明，中草药防己及其主要提取物， 粉防己碱(Tet)对小鼠NIHL有明显的保护作用。本草的临床应用 已经表现出良好的长期安全状况。此外，Tet还具有很强的 具有抗氧化和消炎的特性，还可以阻断钙通道，从而 针对NIHL背后的三个主要信号通路。与资金来源一致 在第一阶段，国家补充和综合健康中心的优先事项 应用，我们将测定该草药提取物的半数有效剂量(ED50)以 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 每天工作时间)与大多数工业工作环境相似。创新方面 我们的方法是：(1)开发一种针对NIHL的营养制剂，从而打破主要的 客户访问障碍，他们更有可能去看听力专家进行听力检查 治疗；(2)在累积噪声暴露与之类似的大鼠模型中进行测试 工厂工人遇到的问题；(3)选择具有良好特性的草本植物 药理特性和长期的临床应用安全历史； 靶向NIHL背后的多个信号通路。如果这项研究的结果是 成功后，我们将获得院校评审委员会(IRB)的批准，进行SBIR 这种营养食品对NIHL的人体第二阶段研究。我们节目的目标是 是将这种营养食品推向市场，用于预防和治疗NIHL。如果 这种方法是成功的，类似的营养食品将被评估其潜力 预防老年性耳聋。