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

• 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
• 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

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）：由受伤、手术或疾病引起的急性和慢性疼痛每年折磨着100亿美国人，对情绪、心理健康和生活质量产生严重影响，每年给美国造成约6000亿美元的经济损失。对许多患者来说，由于现有治疗方法的缺点，治疗方案不能提供足够的缓解。迄今为止，大多数治疗疼痛的方法都是小分子化合物，它们可以阻断选定的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。这些局限性促使人们重新寻找治疗疼痛的新靶点，以及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释放引发疼痛的主要介质，靶向P2X3的药物可能有效治疗慢性疼痛。在这里，我们建议开发针对P2X3离子通道的单克隆抗体来治疗神经性和炎症性疼痛。