Development of P2X3 Ion Channel MAbs for the Treatment of Pain

描述(由申请人提供)：每年有1亿美国人因受伤、手术或疾病引起的急性和慢性疼痛，严重影响情绪、心理健康和生活质量，每年给美国造成约6,000亿美元的经济损失。对于许多患者来说，由于现有治疗方法的缺点，治疗方案无法提供足够的缓解。到目前为止，大多数治疗疼痛的药物都是小分子化合物，它们可以阻断选定的离子通道或其他疼痛受体的活性，但这些治疗药物往往会因非靶点结合而导致副作用或生物利用度较低。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离子通道是由ATP释放引发的疼痛的主要介质，靶向P2X3的药物可能对慢性疼痛有效。在这里，我们建议开发针对离子通道P2X3的单抗，用于治疗神经病理性和炎症性疼痛。

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.