Johnson E A
Department of Food Microbiology and Toxicology, University of Wisconsin, Madison 53706, USA.
Annu Rev Microbiol. 1999;53:551-75. doi: 10.1146/annurev.micro.53.1.551.
Toxins are increasingly being used as valuable tools for analysis of cellular physiology, and some are used medicinally for treatment of human diseases. In particular, botulinum toxin, the most poisonous biological substance known, is used for treatment of a myriad of human neuromuscular disorders characterized by involuntary muscle contractions. Since approval of type-A botulinum toxin by the US Food and Drug Administration in December 1989 for three disorders (strabismus, blepharospasm, and hemifacial spasm), the number of indications being treated has increased greatly to include numerous focal dystonias, spasticity, tremors, cosmetic applications, migraine and tension headaches, and other maladies. Many of these diseases were previously refractory to pharmacological and surgical treatments. The remarkable therapeutic utility of botulinum toxin lies in its ability to specifically and potently inhibit involuntary muscle activity for an extended duration. The clostridia produce more protein toxins than any other bacterial genus and are a rich reservoir of toxins for research and medicinal uses. Research is underway to use clostridial toxins or toxin domains for drug delivery, prevention of food poisoning, and the treatment of cancer and other diseases. The remarkable success of botulinum toxin as a therapeutic agent has created a new field of investigation in microbiology.
毒素正越来越多地被用作分析细胞生理学的宝贵工具,有些毒素还被用于治疗人类疾病。特别是肉毒杆菌毒素,它是已知毒性最强的生物物质,被用于治疗多种以不自主肌肉收缩为特征的人类神经肌肉疾病。自1989年12月美国食品药品监督管理局批准A型肉毒杆菌毒素用于治疗三种疾病(斜视、眼睑痉挛和半面痉挛)以来,其治疗适应症的数量大幅增加,包括许多局灶性肌张力障碍、痉挛、震颤、美容应用、偏头痛和紧张性头痛以及其他疾病。这些疾病中有许多以前对药物和手术治疗均无反应。肉毒杆菌毒素显著的治疗效用在于其能够在较长时间内特异性且有效地抑制不自主肌肉活动。梭菌属产生的蛋白质毒素比其他任何细菌属都多,是用于研究和药用的毒素的丰富来源。目前正在进行研究,以利用梭菌毒素或毒素结构域进行药物递送、预防食物中毒以及治疗癌症和其他疾病。肉毒杆菌毒素作为一种治疗剂的显著成功在微生物学领域开创了一个新的研究方向。