Accelerated Discovery and Development of New Pain Therapeutics

加速新疼痛疗法的发现和开发

• 批准号: 8079538
• 负责人: Tage Honore
• 金额: $ 130.84万
• 依托单位: AESTUS THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-30 至 2012-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8079538
• 关键词: Absence of pain sensation; Acquired Immunodeficiency Syndrome; Acute; Address; Adverse effects; Adverse event; Analgesics; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Antiepileptic Agents; Area; Blood specimen; Burning Pain; Businesses; Capital; Chronic low back pain; Clinic; Clinical; Clinical Research; Development; Diabetes Mellitus; Diabetic Neuropathies; Diagnosis; Disabled Persons; Dose; Dose-Limiting; Drug Kinetics; Esthesia; Evaluation; Exanthema; Future; Goals; Grant; Healthcare; Herpes zoster disease; Hour; Hyperalgesia; Individual; Japan; Laboratories; Lead; Licensing; Lidocaine; Malignant Neoplasms; Marketing; Measures; Mechanics; Methods; Modeling; Monitor; N-Methylaspartate; Neuropathy; Non-Insulin-Dependent Diabetes Mellitus; Norepinephrine; Opioid; Outcome Study; Pain; Pathway interactions; Patients; Pharmaceutical Preparations; Pharmacodynamics; Pharmacologic Substance; Pharmacotherapy; Phase; Phase II Clinical Trials; Physical Examination; Physicians; Placebos; Plasma; Postherpetic neuralgia; Process; Refractory; Reporting; Research Design; Research Methodology; Resistance; Resolution; Resources; Risk; Running; Safety; Schedule; Seizures; Serotonin; Serum; Severities; Skin; Small Business Innovation Research Grant; Societies; Staging; Stimulus; Surface; Symptoms; Tactile; Tactile Hyperalgesias; Technology; Testing; Therapeutic; Therapeutic Agents; Time; Touch sensation; Toxic effect; Treatment Protocols; Tricyclic Antidepressive Agents; Trigeminal Neuralgia; United States; Virus Diseases; Work; allodynia; base; cancer complication; channel blockers; clinically significant; design; drug discovery; drug market; effective therapy; efficacy trial; improved; inhibitor/antagonist; instrument; mechanical allodynia; member; novel; novel strategies; novel therapeutics; painful neuropathy; public health relevance; response; reuptake; success; therapeutic target; treatment duration

DESCRIPTION (provided by applicant): Neuropathic pain is a common complication of cancer, diabetes mellitus, viral infections, and other causes. Although physicians currently employ a variety of treatments to manage moderate to severe neuropathic pain, including non-steroidal anti-inflammatory drugs, opioids, tricyclic antidepressants, anti- seizure medications, serotonin-norepinephrine reuptake inhibitors, and others, many patients are still inadequately treated. The poor success with the currently approved agents has been attributed to both inadequate efficacy and dose limiting toxicity. This unmet clinical need has generated numerous efforts to identify novel therapeutic agents for the treatment of neuropathic pain, but most of these efforts have focused on identifying additional members of drug classes that have previously shown to have some efficacy in this area. Not surprisingly, many of these agents offer little improvement over what is already in use. By means of our proprietary technology, Aestus Therapeutics has identified new classes of substances that may prove effective in treating neuropathic pain by means of novel mechanisms. This approach is particularly promising for targeting the high percentage of patients who are refractory to established therapies. While there are many causes of neuropathic pain, postherpetic neuralgia (PHN) is a particularly useful model for investigating novel analgesic agents. PHN is commonly defined as persistence of the pain associated with herpes zoster for more than three months after resolution of the herpes zoster rash. In the United States more than one million new cases of herpes zoster are reported each year. The pain associated with PHN is typically moderately severe and poorly responsive to established therapies. The focus of our proposal is to conduct a clinical phase 2a proof of principle study to determine whether one of the identified products is likely to be effective at improving PHN pain when administered over a seven day period. A positive outcome of the study will enable us to commercialize the product by partnering with a large pharmaceutical company for late stage clinical studies, filing New Drug Application at FDA and market the product to the benefit of patients and society. PUBLIC HEALTH RELEVANCE: Neuropathic pain patients tend to become globally disabled and are heavy users of healthcare resources. Current therapies have limited efficacy and issues with side effects. By means of our proprietary technology a new class of compounds has been identified that may prove effective in treating neuropathic pain by means of novel mechanisms. This approach is particularly promising for targeting the high percentage of patients who are refractory to established therapies. The focus of the present project is to establish proof of concept in the clinic, focusing on patients suffering postherpetic neuralgia.

描述（由申请人提供）： 神经性疼痛是癌症、糖尿病、病毒感染和其他原因的常见并发症。尽管医生目前采用多种治疗方法来治疗中度至重度神经性疼痛，包括非甾体类抗炎药、阿片类药物、三环类抗抑郁药、抗癫痫药物、5-羟色胺-去甲肾上腺素再摄取抑制剂等，但许多患者仍然没有得到充分的治疗。目前批准的药物效果不佳的原因是功效不足和剂量限制性毒性。这种未满足的临床需求引发了许多努力来确定用于治疗神经性疼痛的新型治疗剂，但这些努力中的大多数都集中在确定先前已证明在该领域具有一定功效的药物类别的其他成员。毫不奇怪，这些药物中的许多与已经使用的药物相比几乎没有什么改进。借助我们的专有技术，Aestus Therapeutics 已经确定了新类别的物质，这些物质可能通过新机制有效治疗神经性疼痛。这种方法特别有希望针对高比例的对既定疗法无效的患者。虽然神经性疼痛的原因有很多，但带状疱疹后神经痛 (PHN) 是研究新型镇痛药特别有用的模型。 PHN 通常被定义为带状疱疹皮疹消退后，与带状疱疹相关的疼痛持续三个月以上。在美国，每年报告的带状疱疹新病例超过一百万例。与 PHN 相关的疼痛通常为中度严重，并且对现有疗法反应不佳。我们提案的重点是进行临床 2a 期原理证明研究，以确定其中一种已确定的产品在 7 天的时间内服用是否可能有效改善 PHN 疼痛。该研究的积极成果将使我们能够通过与一家大型制药公司合作进行后期临床研究、向 FDA 提交新药申请并将该产品推向市场，从而使该产品商业化，造福患者和社会。 公共卫生相关性： 神经性疼痛患者往往会导致全球残疾，并且是医疗资源的大量使用者。目前的疗法疗效有限且存在副作用问题。通过我们的专有技术，已经鉴定出一类新的化合物，这些化合物可能通过新机制有效治疗神经性疼痛。这种方法对于针对高比例的对现有疗法难治的患者特别有希望。本项目的重点是在临床上建立概念验证，重点关注患有带状疱疹后神经痛的患者。