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（持续疼痛超过三个月）。对经常高度衰弱的慢性疼痛的有效治疗是有限的和有问题的：最常见的处方药是阿片类药物（如可待因，芬太尼，吗啡），具有严重的副作用 *。为了解决缺乏安全，非成瘾性和有效的止痛药治疗慢性疼痛的问题，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称为Nav1.7\的离子通道驱动和维持。通过选择性地阻断慢性疼痛中发现的Nav1.7的持续过度激活，我们的目标是减轻这种使人衰弱的状况。狼蛛的毒液包括一种小的“打结”蛋白，已知它可以阻断Nav1.7。这种狼蛛衍生的“knottin”蛋白不适合作为治疗剂，因为它在体内表现出不希望的交叉反应性，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在抗体的识别表面内，创造了一种杂交分子（“结体”）。该KnotBody旨在解决从血液中快速清除和不必要的交叉反应性问题。通过这笔资金，IONTAS将把我们现有的原型KnotBody分子开发成一种更安全、有效和更特异性的候选药物，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."