Development of P2X3 Ion Channel MAbs for the Treatment of Pain

开发用于治疗疼痛的 P2X3 离子通道单克隆抗体

基本信息

批准号：
9130898
负责人：
JOSEPH Benjamin RUCKER
金额：
$ 21.53万
依托单位：
INTEGRAL MOLECULAR
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-02-01 至 2018-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9130898
关键词：
Acute Pain Address Adverse effects Afferent Neurons Affinity American Antibodies Antibody Specificity Antigens Avidity Binding Binding Sites Biological Assay Biological Availability Biosensor Cell Line Clinical Complex Data Degenerative polyarthritis Development Disease Drug Targeting Engineering Epitope Mapping Epitopes Family member Feedback Formulation Future Goals Health Human Hydrophobicity Immunization Immunoglobulin G Individual Inflammation Inflammatory Injury Integral Membrane Protein Ion Channel Kinetics Lead Living Costs Measures Mediator of activation protein Membrane Proteins Mental Health Modeling Molecular Monoclonal Antibodies Moods Mutagenesis Neuropathy Operative Surgical Procedures P2X-receptor Pain Pain management Patients Phase Probability Production Public Health Publications Quality of life Rattus Safety Serum Shotguns Signal Transduction Specificity Staging Techniques Technology Testing Therapeutic Therapeutic Monoclonal Antibodies Time Tissue Microarray base chronic constriction injury chronic pain commercialization cross reactivity economic cost efficacy testing human disease human tissue immunogenicity improved in vivo inflammatory neuropathic pain inhibitor/antagonist meetings nerve injury novel pain receptor phase 1 study preclinical study response small molecule small molecule inhibitor success therapeutic development

项目摘要

DESCRIPTION (provided by applicant): Acute and chronic pain resulting from injury, surgery, or disease afflicts >100 million Americans each year, having a severe impact on mood, mental health, and quality of life and costing the U.S. approximately $600 billion in economic costs annually. For many patients, treatment options provide inadequate relief because of the shortcomings of available therapeutics. To date, most treatments for pain have been small molecule compounds that block the activity of select ion channels or other pain receptors, but these therapeutics often result in side-effects caused by off-target binding or suffer from poor bioavailability. These limitations have prompted renewed searches for novel targets for the treatment of pain and novel types of inhibitors capable of achieving the specificity and bioavailability needed for a successful therapeutic. The P2X3 ion channel is a primary mediator of pain triggered by ATP release, and drugs that target P2X3 could be efficacious in treating chronic pain. Here we propose to develop MAbs targeting the ion channel P2X3 for the treatment of neuropathic and inflammatory pain.

描述（由申请人提供）：每年有超过 1 亿美国人遭受由伤害、手术或疾病引起的急性和慢性疼痛，对情绪、心理健康和生活质量产生严重影响，并给美国造成约 6000 亿美元的经济损失每年的费用。对于许多患者来说，由于现有疗法的缺点，治疗方案无法充分缓解症状。迄今为止，大多数疼痛治疗方法都是小分子化合物，它们会阻断选择性离子通道或其他疼痛受体的活性，但这些治疗方法通常会导致脱靶结合引起的副作用或生物利用度差。这些限制促使人们重新寻找治疗疼痛的新靶点和能够实现成功治疗所需的特异性和生物利用度的新型抑制剂。 P2X3 离子通道是 ATP 释放引发的疼痛的主要介质，针对 P2X3 的药物可有效治疗慢性疼痛。在此，我们建议开发针对离子通道 P2X3 的单克隆抗体，用于治疗神经性疼痛和炎性疼痛。