Dissecting pain pathways with conopeptides

发展更安全、更有效的疼痛治疗的一个主要障碍是慢性疼痛涉及的不同途径的性质定义不清。申请团队汇集了一套独特的研究专业知识，利用神经毒素在分子水平上定义神经系统的功能。申请者还对了解和改进疼痛的治疗，特别是慢性疼痛的治疗有着共同的兴趣，通过专注于疼痛研究，该计划将显著扩大顺刘易斯·艾尔伍德、亚当斯和克里斯蒂之间现有的多学科合作的范围，这些合作已经在药理学和神经科学领域产生了相当大的影响。独联体还在疼痛治疗药物的开发方面拥有相当丰富的经验，发现了两种目前正在与AMRAD(AM336)和Xenome Ltd(Xen2174)进行商业开发的螺杆菌多肽。该计划将发现并使用此类高度选择性的柯多肽，以剖析外周疼痛通路的药理作用及其向中枢神经系统的投射，并识别和表征可用于药物干预的新靶点。该计划的长期目标是在疼痛通路中发现新的靶点，并开发在慢性疼痛动物模型中作用于这些靶点的螺杆菌多肽。这些分子将在该计划中进行优化，以使它们可以考虑与商业合作伙伴合作进行临床前开发。

A major obstacle to the development of safer and more effective pain treatments is the poorly defined nature of the different pathways involved in chronic pain. The applicant team bring together a unique set of research expertise in using neurotoxins to define, at the molecular level, how the nervous system functions. The applicants also share a common interest in understanding and improving treatments for pain, especially chronic pain which continues to remain poorly managed Through a focus on pain research, the Program will significantly enhance the scope of existing multidisciplinary collaborations between the Cis Lewis Alewood, Adams and Christie, which have already made a considerable impact in the fields of pharmacology and neuroscience. The CIs also have considerable experience in the development of pain therapeutics, having discovered two conopeptides now under commercial development with AMRAD (AM336) and Xenome Ltd (Xen2174). This Program will discover and use highly selective conopeptides such as these to dissect the pharmacology of peripheral pain pathways and their projections into the central nervous system, and to identify and characterise new targets amenable to drug intervention. The long-term goal of the Program is to discover new targets in pain pathways and develop conopeptides that act on these targets in animal models of chronic pain. These molecules will be optimised within the Program to the point where they can be considered for pre-clinical development in collaboration with commercial partners.