Development of P2X3 Ion Channel MAbs for the Treatment of Pain

摘要 由损伤、手术或疾病引起的急性和慢性疼痛折磨着超过1亿美国人 每年，对情绪，心理健康和生活质量产生严重影响， 美国每年约6000亿美元的经济成本。对于许多患者来说，治疗 由于可用治疗剂的缺点，这些选择提供的缓解不充分。到 迄今为止，大多数疼痛治疗都是小分子化合物， 选择离子通道或其他疼痛受体，但这些疗法通常会导致副作用 由脱靶结合引起或遭受差的生物利用度。这些限制促使 重新寻找治疗疼痛的新靶点和新型抑制剂 能够达到成功治疗所需的特异性和生物利用度。的 P2X3离子通道是由ATP释放触发的疼痛的主要介质，并且靶向P2X3离子通道的药物是 P2X3可能在治疗慢性疼痛中有效。在这里，我们建议开发针对 离子通道P2X3用于治疗神经性疼痛和炎性疼痛。

ABSTRACT 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.