New non-paralytic botulinum molecules for the control of pain

在动物和人类的生活中，意外事故或手术干预等事件都可能导致无法控制的疼痛，这种疼痛在最初的伤害之后会持续很长时间。这是一种慢性疼痛，治疗方法尚待解决——19%的欧洲成年人患有中度至重度慢性疼痛；不到60%的患者接受了适当的疼痛缓解。新的治疗方法是必需的，但开发这些需要新的治疗方法，并更好地了解疼痛途径中出现的问题，导致无法控制的疼痛。利用我们最近对肉毒杆菌分子的研究结果，结合我们对疼痛机制的现有知识，我们将有选择地沉默来自皮肤和其他身体组织的疼痛纤维以及脊髓中特定神经细胞的疼痛信号。肉毒杆菌分子是由肉毒杆菌产生的一种蛋白质和神经毒素。肉毒杆菌分子可引起弛缓性神经肌肉麻痹，这是一种危及人类和动物生命的严重疾病。它的商品名之一肉毒杆菌素广为人知，用于各种美容和医疗程序。然而，我们已经找到了一种方法，将肉毒杆菌分子的麻痹效应与它对其他神经元的沉默效应分离开来。通过使用这种新的合成化学物质，我们将靶向并抑制特定的神经元群，从而缓解慢性疼痛状态。本应用程序中概述的实验将使我们能够迅速走向临床，并将这些新的肉毒杆菌衍生物应用于不同类型的慢性疼痛。例如，可以想象，将我们的一种肉毒杆菌结构注射到患有关节炎的疼痛关节或骨癌疼痛患者的脊髓上，可以减轻疼痛，而不会产生麻木或瘫痪。

In both animals and humans life events such as accidents or surgical interventions can lead to uncontrollable pain that can persist long after the original injury. This is chronic pain, the treatment of which is yet to be resolved - 19% of adult Europeans suffer from chronic pain of moderate to severe intensity; less than 60% receive adequate pain relief. New treatments are required but to develop these requires new therapeutic approaches and a better understanding of what goes wrong in the pain pathways resulting in uncontrollable pain. Using the results of our recent research on Botulinum molecules, together with our existing knowledge of pain mechanisms, we will selectively silence pain signals both in pain fibers from the skin and other body tissues as well as in specific nerve cells in the spinal cord. Botulinum molecule is a protein and neurotoxin produced by the bacterium Clostridium botulinum. Botulinum molecule can cause flaccid neuromuscular paralysis, a serious and life-threatening illness in humans and animals. Popularly known by one of its trade names, Botox, it is used for various cosmetic and medical procedures. However we have found a way to separate the paralysing effects of the botulinum molecule from its silencing effects on other neurons. By using this new synthetic chemistry we will target and silence specific populations of neurons reversibly and alleviate chronic pain states.The experiments outlined in this application will allow us to move rapidly towards the clinic and to apply these new Botulinum derivatives to different types of chronic pain. For example it is possible to imagine that a single injection of one of our Botulinum constructs into a painful arthritic joint or over the spinal cord of a patient with bone cancer pain would ameliorate pain without generating numbness or paralysis.