Experimental therapeutics for dystonia

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.