Development of a Novel Cancer Pain Therapeutic

描述（由申请人提供）：开发一种新型癌症疼痛治疗剂癌症引起的疼痛是疾病进展中最大的恐惧之一，有时甚至比死亡还要大。许多研究表明，疼痛在晚期病例中占优势。但更糟糕的是，很多时候这种疼痛是最后一种治疗方法：阿片类药物。我们设计的重组靶向毒素，物质P-皂草素（SP-SAP），并显示出选择性毒性NK 1 R轴承神经元。单次鞘内（IT）输注SP-SAP减轻了大鼠和犬的病理性疼痛感知，而不影响其他感觉信号通路。在与美国食品药品监督管理局（FDA）的IND前讨论中，SP-SAP被认为是治疗阿片类药物难治性癌症疼痛患者的重要新方法。该提案的具体目标旨在回应FDA的要求，为研究性新药申请做准备，并在阿片类药物难治性疼痛的癌症患者中完成1/2期临床试验。已经组建了一个具有完成这些具体目标的专业知识的顶级团队。这里提出的研究将提供关键信息，导致关键的临床试验和最终商业化的一个完全创新的治疗癌症疼痛。 公共卫生相关性：一种新型癌症疼痛治疗方法的开发癌症引起的疼痛是疾病进展中最大的恐惧之一，有时甚至比死亡还要大。这里提出的研究将提供关键信息，导致关键的临床试验和最终商业化的一个完全创新的治疗癌症疼痛。

DESCRIPTION (provided by applicant): Development of a Novel Cancer Pain Therapeutic Pain due to cancer is one of the great fears, at times greater than even death, in the progression of the disease. Numerous studies have shown the preponderance of pain in terminal cases. But even worse, many times this pain is refractory to the last stand treatment: opioids. We engineered the recombinant targeted toxin, substance P-saporin (SP-SAP) and showed selective toxicity to NK1R- bearing neurons. A single intrathecal (IT) infusion of SP-SAP alleviated pathologic pain perception without affecting other sensory signal pathways in rats and dogs. In pre-IND discussions with the Food and Drug Administration (FDA), SP-SAP was considered to be an important new approach for the treatment of cancer pain in patients refractory to opioids. Specific Aims for this proposal are designed to respond to requests from the FDA, prepare for an Investigative New Drug Application and complete a Phase 1/2 clinical trial in cancer patients with pain that is refractory to opioids. A top level team of groups with the expertise to complete these Specific Aims has been assembled. The studies proposed here will provide critical information leading to pivotal clinical trials and eventual commercialization of a completely innovative therapy for cancer pain. PUBLIC HEALTH RELEVANCE: Development of a Novel Cancer Pain Therapeutic Pain due to cancer is one of the great fears, at times greater than even death, in the progression of the disease. The studies proposed here will provide critical information leading to pivotal clinical trials and eventual commercialization of a completely innovative therapy for cancer pain.