Creating novel Nav1.7 inhibiting antibodies for the treatment of chronic pain

三分之一的成年人会经历慢性疼痛(持续三个月以上的疼痛)。对经常使人虚弱的慢性疼痛的有效治疗是有限的和有问题的：最常用的处方药物是阿片类药物(例如可待因、芬太尼、吗啡)，它们有严重的副作用**。**为了解决缺乏安全、非成瘾和有效的慢性疼痛止痛药的问题，IONTAS旨在开发一种替代的、非阿片类药物。神经系统中的疼痛信号由一种名为Nav1.7的离子通道驱动和维持。通过选择性地阻断在慢性疼痛中发现的持续的、过度激活的Nav1.7，我们的目标是缓解这种虚弱的状况。狼蛛的毒液中含有一种已知可以阻止Nav1.7的小结蛋白。这种从狼蛛中提取的“结”蛋白不适合作为治疗药物，因为它在体内表现出不必要的交叉反应，并迅速从血液循环中清除。我们通过将这种狼蛛结蛋白融合到抗体的识别表面，创造了一种杂交分子(“结体”)。这种结体的设计是为了解决快速从血液中去除和不必要的交叉反应的问题。通过这笔资金，IONTAS将把我们现有的结体分子原型开发成一种更安全、有效和更具体的候选药物，旨在改善慢性疼痛患者的生活质量，同时为日益严重的全球阿片类药物危机提供解决方案。“

"One in three adults will experience chronic pain (persistent pain lasting more than three months). Effective treatment for often highly debilitating chronic pain is limited and problematic: the most commonly prescribed medications are opioids (e.g. codeine, fentanyl, morphine) which have serious side-effects**.**To address the lack of safe, non-addictive and effective pain-killers for chronic pain, IONTAS aims to develop an alternative, non-opioid medication. Pain signalling in the nervous system is driven and maintained by an ion channel called Nav1.7\. By selectively blocking the persistent, over-activation of Nav1.7 found in chronic pain we aim to alleviate this debilitating condition.The venom of a tarantula includes a small ""knotted"" protein that is known to block Nav1.7\. This tarantula-derived ""knottin"" protein is unsuitable as a therapeutic since it exhibits unwanted cross-reactivity in the body and is rapidly removed from the blood circulation. We have created a hybrid molecule (a ""KnotBody"") by fusing this tarantula knottin within the recognition surface of an antibody. This KnotBody is designed to address the problems of rapid removal from the blood and unwanted cross-reactivity. Through this funding, IONTAS will develop our existing prototype KnotBody molecules into a safer, effective and more specific drug candidate aimed at improving the quality of life of chronic pain patients whilst providing a solution to the growing, global opioid crisis."