Experimental pharmacology: Targeting metabolic pathways.

Abstract

Since the discovery of the treatment for Wilson disease a growing number of treatable inherited dystonias have been identified and their search and treatment have progressively been implemented in the clinics of patients with dystonia. While waiting for gene therapy to be more widely and adequately translated into the clinical setting, the efforts to divert the natural course of dystonia reside in unveiling its pathogenesis. Specific metabolic treatments can rewrite the natural history of the disease by preventing neurotoxic metabolite accumulation or interfering with the cell accumulation of damaging metabolites, restoring energetic cell fuel, supplementing defective metabolites, and supplementing the defective enzyme. A metabolic derangement of cell homeostasis is part of the progression of many non-metabolic genetic lesions and could be the target for possible metabolic approaches. In this chapter, we provided an update on treatment strategies for treatable inherited dystonias and an overview of genetic dystonias with new experimental therapeutic approaches available or close to clinical translation.