Accelerated Discovery and Development of New Pain Therapeutics

加速新疼痛疗法的发现和开发

• 批准号: 7326583
• 负责人: LILLIAN W CHIANG
• 金额: $ 19.9万
• 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 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7326583
• 关键词: Address; Adverse effects; Affect; Alcoholism; Amputation; Analgesics; Animal Model; Animals; Antiepileptic Agents; Biological; Characteristics; Chemistry; Chronic; Clinical; Clinical Data; Clinical Research; Data; Data Analyses; Data Set; Databases; Development; Diabetes Mellitus; Disabled Persons; Disease; Disease Progression; End Point; Gene Expression; Genes; Genome; Goals; Healthcare; Housing; Injury; Internet; Investments; Journals; Laboratories; Lead; Legal patent; Licensing; Lidocaine; Ligation; Malignant Neoplasms; Mediation; Methods; Modeling; Multiple Sclerosis; N-Methylaspartate; Opioid; Outsourcing; Pain; Pathway interactions; Patients; Personal Satisfaction; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacology; Pharmacotherapy; Phase; Phase I Clinical Trials; Process; Property; Public Domains; Publications; Purpose; Rattus; Research Infrastructure; Research Personnel; Resistance; Resources; Risk; Site; Small Business Funding Mechanisms; Small Business Innovation Research Grant; Spinal cord injury; Spinal nerve structure; Staging; Structure; Surveys; Technology; Testing; Therapeutic; Therapeutic Index; Time; Triage; Tricyclic Antidepressive Agents; United States; Validation; Vitamin Deficiency; base; clinically significant; concept; desire; drug discovery; drug testing; efficacy trial; innovation; insight; man; novel; painful neuropathy; pre-clinical; research study; response; tool

DESCRIPTION (provided by applicant): More than 25 million people in the United States suffer from neuropathic pain. Currently available drugs include opioids, anti-epileptics, topicals such as lidocaine, NMDA antagonists, and tricyclic antidepressants, none of which achieve clinical significance greater than 50%. To address this problem of significant clinical need and poor clinical significance, new mechanisms of action must be identified for pain therapeutics. Genome-scale technologies such as gene expression microarray data have contributed an exponential amount of diverse biological information available to the public. The goal of this project is to analyze this data to generate new understanding of underlying biological mechanisms which can lead directly to a marketable pain therapeutic. Recently, many researchers have extracted biological pathway information from gene expression microarray experiments performed in-house. In order to take advantage of the much more diverse information contained in public microarray data, this proposal tests the feasibility of new methods to combine unstructured information from multiple public datasets to derive new insight on biological pathways underlying neuropathic pain. Newly associated pathway information is used to identify therapeutics which affect the identified pathway and which have been tested in man, but whose mechanism of action has not been previously associated with pain. The identified drugs will be validated in animal models. Since the identified therapeutic by definition is an IND, successful demonstration of efficacy in animals will lead directly to clinical phase 2 proof of concept in man during the SBIR Phase II renewal. Thus this project proposes a method to significantly reduce drug discovery and early development risk by triaging public gene expression data to progress directly to product identification and late stage clinical studies for pain therapeutics with new mechanisms of action. 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. The present project proposes a method to significantly reduce drug discovery and early development risk by triaging public gene expression data to progress directly to product identification and late stage clinical studies for pain therapeutics with new mechanisms of action.

描述(申请人提供)：美国有2500多万人患有神经性疼痛。目前可用的药物包括阿片类药物、抗癫痫药物、利多卡因、NMDA拮抗剂和三环类抗抑郁药等局部药物，这些药物的临床意义都没有达到50%以上。为了解决这一重大的临床需求和较差的临床意义的问题，必须确定疼痛治疗的新作用机制。基因组规模的技术，如基因表达微阵列数据，为公众提供了指数级数量的多样化生物信息。这个项目的目标是分析这些数据，以产生对潜在生物学机制的新理解，这可能直接导致市场上的疼痛治疗。最近，许多研究人员从内部进行的基因表达微阵列实验中提取了生物途径信息。为了利用公共微阵列数据中包含的更多样化的信息，该提案测试了新方法的可行性，以组合来自多个公共数据集的非结构化信息，以获得对神经病理性疼痛潜在的生物路径的新见解。新关联的通路信息被用来识别影响已识别通路的治疗方法，这些疗法已经在人类身上进行了测试，但其作用机制以前从未与疼痛有关。识别出的药物将在动物模型中得到验证。由于根据定义确定的治疗方法是IND，在动物身上成功证明疗效将直接导致在SBIR第二阶段更新期间对人类进行第二阶段的临床概念验证。因此，该项目提出了一种方法，通过对公共基因表达数据进行分类，直接进行具有新作用机制的止痛药的产品鉴定和后期临床研究，从而显著降低药物发现和早期开发风险。神经病理性疼痛患者往往会在全球范围内致残，并大量使用医疗资源。目前的治疗方法疗效有限，且存在副作用问题。本项目提出了一种方法，通过对公共基因表达数据进行分类，直接进行具有新作用机制的止痛药的产品鉴定和后期临床研究，从而显著降低药物发现和早期开发风险。