Drug Development of a Chronic Pain Therapeutic

描述(申请人提供)：SP-SAP是多肽神经递质P物质和核糖体失活蛋白Saporin的结合物，通过先前NIH的资助，已经被证明可以在几个大鼠模型中消融慢性疼痛传递。重要的是，敏锐的、反射性的痛觉仍然完好无损。这种结合物在鞘内注射后，通过消除脊髓背角浅层少量P物质受体表达的神经元起作用。美国食品和药物管理局建议，这种药物的初始患者群体是对阿片类药物无效的晚期癌症患者。本申请的目的是获得资金，通过建立良好制造规范(GMP)级别的SP-SAP并按照FDA的要求在大鼠和狗身上进行毒理学/安全性研究来服用SP-SAP，从而使该药物更接近临床试验。请拨资金用于设备，以完成GMP级设施，用于合成用于毒理学/安全性的SP-SAP(非GMP级)，用于实际毒理学/安全性研究(将分包)，以及用于编制满足食品和药物管理局关于GMP材料要求的议定书。最后，将合成GMP级SP-SAP，为临床试验做准备。

DESCRIPTION (provided by applicant): SP-SAP, a conjugate between the peptide neurotransmitter substance P, and the ribosome-inactivating protein, saporin, has been shown, through previous NIH funding, to ablate chronic pain transmission in several rat models. Importantly, acute, reflexive pain perception remains intact. The conjugate acts by elimination of the small number of substance P receptor-expressing neurons in the superficial laminae of the dorsal horn of the spinal cord after intrathecal injection. The Food and Drug Administration has recommended that the initial patient population for this drug be terminal cancer patients in pain that is refractory to opioids. The purpose of this application is to obtain funding to move this drug closer to clinical trial by establishing Good Manufacturing Practice (GMP)-grade SP-SAP and by taking SP-SAP through toxicology/safety studies in the rat and the dog, as requested by the FDA. Funding is requested for equipment to complete a GMP-level facility, for synthesis of SP-SAP for toxicology/safety (not at GMP level), for the actual toxicology/safety studies (that will be sub-contracted) and for the preparation of protocols that satisfy the FDA request for GMP materials. Finally, GMP-grade SP-SAP will be synthesized in preparation for clinical trial.