Jinnah H A, Hess Ellen J
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
Neurotherapeutics. 2008 Apr;5(2):198-209. doi: 10.1016/j.nurt.2008.01.001.
Dystonia is a neurological syndrome characterized by excessive involuntary muscle contractions leading to twisting movements and unnatural postures. It has many different clinical manifestations, and many different causes. More than 3 million people worldwide suffer from dystonia, yet there are few broadly effective treatments. In the past decade, progress in research has advanced our understanding of the pathogenesis of dystonia to a point where drug discovery efforts are now feasible. Several strategies can be used to develop novel therapeutics for dystonia. Existing therapies have only modest efficacy, but may be refined and improved to increase benefits while reducing side effects. Identifying rational targets for drug intervention based on the pathogenesis of dystonia is another strategy. The surge in both basic and clinical research discoveries has provided insights at all levels, including etiological, physiological and nosological, to enable such a targeted approach. The empirical approach to drug discovery, whereby compounds are identified using a nonmechanistic strategy, is complementary to the rational approach. With the recent development of multiple animal models of dystonia, it is now possible to develop assays and perform drug screens on vast numbers of compounds. This multifaceted approach to drug discovery in dystonia will likely provide lead compounds that can then be translated for clinical use.
肌张力障碍是一种神经综合征，其特征为肌肉过度不自主收缩，导致扭曲动作和不自然姿势。它有许多不同的临床表现和多种不同病因。全球有超过300万人患有肌张力障碍，但广泛有效的治疗方法却很少。在过去十年中，研究进展使我们对肌张力障碍的发病机制有了深入了解，从而使药物研发工作成为可能。可采用多种策略来开发治疗肌张力障碍的新型疗法。现有疗法疗效有限，但可加以改进和完善，以增加益处并减少副作用。基于肌张力障碍的发病机制确定合理的药物干预靶点是另一种策略。基础研究和临床研究发现的激增在病因学、生理学和疾病分类学等各个层面都提供了见解，从而能够采用这种靶向方法。通过非机械策略鉴定化合物的经验性药物研发方法与合理方法相辅相成。随着近期多种肌张力障碍动物模型的开发，现在有可能开发检测方法并对大量化合物进行药物筛选。这种针对肌张力障碍的多方面药物研发方法可能会提供先导化合物，进而转化为临床应用。
