Preclinical Testing of Tetrandrine against Noise-Induce Hearing Loss

粉防己碱抗噪声性听力损失的临床前测试

基本信息

批准号：
9140718
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：
2016
资助国家：
美国
起止时间：
2016-05-01 至 2017-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9140718
关键词：
Acquired Immunodeficiency Syndrome Acute Address Affect Aftercare Alkaloids American Animal Model Animals Anti-Inflammatory Agents Anti-inflammatory Antiepileptic Agents Antioxidants Auditory Brainstem Responses Benzylisoquinolines CBA/CaJ Mouse Calcium Channel Calcium Channel Blockers Chinchilla (genus)Chinese Herbs Chinese People Clinical Clinical Research Clinical Trials Complex Consult Data Development Dose Drug Kinetics Environmental Hazards Free Radicals Future Goals Hearing Hearing problem Hour Immunodeficiency and Cancer Intervention Intraperitoneal Injections Investigational Drugs Investigational New Drug Application Magic Marketing Measures Medicinal Herbs Modeling Molecular Molecular Target Noise Noise-Induced Hearing Loss Pathway interactions Pharmaceutical Preparations Pharmacodynamics Pharmacotherapy Phase Pre-Clinical Model Preclinical Testing Presbycusis Prevention Process Property Publishing Recording of previous events Safety Signal Pathway Small Business Innovation Research Grant Small Business Technology Transfer Research Suggestion T-Type Calcium Channels Testing Therapeutic Toxic effect United States Food and Drug Administration Work base cellular targeting clinical application combat dosage drug development hearing impairment innovation novel strategies novel therapeutics occupational hazard phase 2 study preclinical study pressure prevent programs prophylactic public health relevance research study sound therapeutic target

项目摘要

DESCRIPTION (provided by applicant): Noise is the most common occupational and environmental hazard, thus it is not surprising that noise-induced hearing loss (NIHL) is the second most common form of sensorineural hearing deficit, second only to age-related hearing loss. Although therapeutics that target the free radical pathway have shown promise for reducing NIHL, there are no medications approved by the U.S. Food and Drug Administration for NIHL. Development of an efficacious treatment has been hampered by the complex array of cellular and molecular pathways involved in NIHL. Therefore, a new approach is necessary to combat these multiple signaling pathways in order for therapeutics to be successful at preventing and treating NIHL. Recent preclinical studies have demonstrated that calcium channel blockers and anti-inflammatory drugs can prevent NIHL. Tetrandrine (TET), a bis-benzylisoquinoline alkaloid originally purified from a Chinese medicinal herb, shows strong promise as a NIHL therapeutic due to its antioxidant and anti-inflammatory properties, as well as its ability to block calcium channels. Moreover, the use of TET clinically has shown a long-term safety profile. Based on our preliminary findings that TET could protect against NIHL, in this Phase I STTR application, we will determine the median effective dose (ED50) for this drug to prevent (Aim 1) and treat (Aim 2) NIHL in two different animal models. The innovative aspects in our approach for using TET are: (1) TET already has well-characterized pharmacological properties and a long history of clinical applications; and (2) TET is known to intervene in multiple signaling pathways involved in NIHL. We will use the data from these studies to complete an Investigational New Drug (IND)-enabling data package for our SBIR phase II clinical studies of this agent. The goal of this program is to bring TET to market for use in prevention and treatment of NIHL.

描述（由申请人提供）：噪声是最常见的职业和环境危害，因此噪声性听力损失 (NIHL) 成为第二常见的感音神经性听力损失，仅次于年龄相关性听力损失也就不足为奇了尽管针对自由基途径的疗法已显示出减少 NIHL 的希望，但美国食品和药物管理局尚未批准用于治疗 NIHL 的有效治疗方法的开发受到复杂的细胞和细胞因子的阻碍。因此，为了使治疗能够成功预防和治疗 NIHL，需要一种新的方法来对抗这些多种信号通路。最近的临床前研究表明，钙通道阻滞剂和抗炎药物可以预防 NIHL。粉防己碱 (TET) 是一种双苄基异喹啉生物碱，最初是从中草药中纯化出来的，由于其抗氧化和抗炎特性，以及作为 NIHL 治疗剂的强大前景。此外，TET 的临床使用已显示出长期安全性。根据我们的初步研究结果，TET 可以预防 NIHL，在这一期 STTR 申请中，我们将确定中位有效剂量。该药物在两种不同动物模型中预防（目标 1）和治疗（目标 2）NIHL 的创新点是：（1）TET 已经具有良好的药理学特性和悠久的历史。 (2) TET 已知可干预 NIHL 涉及的多种信号通路，我们将使用这些研究的数据来完成 SBIR II 期临床研究的研究性新药 (IND) 数据包。该项目的目标是将 TET 推向市场，用于预防和治疗 NIHL。