title: Development of pharmacological strategies for mitochondrial disorders.
abstract: Mitochondrial diseases are an unusually genetically and phenotypically heterogeneous group of disorders, which are extremely challenging to treat. Currently, apart from supportive therapy, there are no effective treatments for the vast majority of mitochondrial diseases. Huge scientific effort, however, is being put into understanding the mechanisms underlying mitochondrial disease pathology and developing potential treatments. To date, a variety of treatments have been evaluated by randomized clinical trials, but unfortunately, none of these has delivered breakthrough results. Increased understanding of mitochondrial pathways and the development of many animal models, some of which are accurate phenocopies of human diseases, are facilitating the discovery and evaluation of novel prospective treatments. Targeting reactive oxygen species has been a treatment of interest for many years; however, only in recent years has it been possible to direct antioxidant delivery specifically into the mitochondria. Increasing mitochondrial biogenesis, whether by pharmacological approaches, dietary manipulation or exercise therapy, is also currently an active area of research. Modulating mitochondrial dynamics and mitophagy and the mitochondrial membrane lipid milieu have also emerged as possible treatment strategies. Recent technological advances in gene therapy, including allotopic and transkingdom gene expression and mitochondrially targeted transcription activator-like nucleases, have led to promising results in cell and animal models of mitochondrial diseases, but most of these techniques are still far from clinical application.
authors.affiliation: Clinical and Molecular Genetics Unit, UCL Institute of Child Health, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Kanabus
authors.forename: S J
authors.initials: SJ
authors.lastname: Heales
authors.forename: S
authors.initials: S
authors.lastname: Rahman
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000187:drug effects; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D028361:Mitochondrial Diseases / Q000188:drug therapy* / Q000628:therapy; D063269:Mitochondrial Turnover / Q000187:drug effects; D008954:Models, Biological; D058990:Molecular Targeted Therapy / Q000379:methods*; D010085:Oxidative Phosphorylation / Q000187:drug effects
chemical_list: D000975:Antioxidants
keywords: clinical trials for mitochondrial disorders; gene therapy for mitochondrial diseases; mitochondrial biogenesis; mitochondrial diseases; models for mitochondrial disorders; nutritional and cofactor support in mitochondrial disorders; treatments for mitochondrial disorders