Development of a Novel Cancer Pain Therapeutic

描述(由申请人提供)：开发一种新的癌症疼痛治疗癌症引起的疼痛是疾病发展过程中最令人恐惧的事情之一，有时甚至比死亡更可怕。许多研究表明，疼痛在临终病例中占主导地位。但更糟糕的是，这种疼痛很多时候对最后一种治疗--阿片类药物--是难治的。我们设计了重组靶向毒素，P-皂苷物质(SP-SAP)，并对NK1R神经元显示出选择性毒性。单次鞘内注射SP-SAP可减轻大鼠和狗的病理性痛觉，而不影响其他感觉信号通路。在IND前与食品和药物管理局(FDA)的讨论中，SP-SAP被认为是治疗阿片类药物无效患者癌痛的重要新方法。这项提案的具体目的是响应FDA的要求，准备一项调查性新药申请，并完成对阿片类药物无效的癌症患者疼痛的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门知识的顶级小组。这里提出的研究将提供关键信息，导致一种治疗癌症疼痛的完全创新疗法的关键临床试验和最终商业化。 公共卫生相关性：开发一种新的癌症疼痛治疗方法癌症引起的疼痛是疾病发展过程中最令人恐惧的问题之一，有时甚至比死亡更可怕。这里提出的研究将提供关键信息，导致一种治疗癌症疼痛的完全创新疗法的关键临床试验和最终商业化。

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.