title: Emerging therapies for mitochondrial disorders.
abstract: Mitochondrial disorders are a diverse group of debilitating conditions resulting from nuclear and mitochondrial DNA mutations that affect multiple organs, often including the central and peripheral nervous system. Despite major advances in our understanding of the molecular mechanisms, effective treatments have not been forthcoming. For over five decades patients have been treated with different vitamins, co-factors and nutritional supplements, but with no proven benefit. There is therefore a clear need for a new approach. Several new strategies have been proposed acting at the molecular or cellular level. Whilst many show promise in vitro, the clinical potential of some is questionable. Here we critically appraise the most promising preclinical developments, placing the greatest emphasis on diseases caused by mitochondrial DNA mutations. With new animal and cellular models, longitudinal deep phenotyping in large patient cohorts, and growing interest from the pharmaceutical industry, the field is poised to make a breakthrough.
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Nightingale
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK Department of Clinical Neurosciences, University of Calgary, Calgary, Canada Hotchkiss Brain Institute, at the University of Calgary, Calgary, Canada.
authors.forename: Gerald
authors.initials: G
authors.lastname: Pfeffer
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK.
authors.forename: David
authors.initials: D
authors.lastname: Bargiela
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK.
authors.forename: Rita
authors.initials: R
authors.lastname: Horvath
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK MRC-Mitochondrial Biology Unit, Cambridge Biomedical Campus, Cambridge, CB2 0XY, UK Department of Clinical Neurosciences, Cambridge Biomedical Campus, University of Cambridge, Cambridge, CB2 0QQ, UK pfc25@medschl.cam.ac.uk.
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Chinnery
mesh_terms: D000818:Animals; D004272:DNA, Mitochondrial / Q000235:genetics; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D028361:Mitochondrial Diseases / Q000188:drug therapy* / Q000235:genetics / Q000601:surgery; D008954:Models, Biological; D058990:Molecular Targeted Therapy / Q000379:methods*; D009154:Mutation; D033581:Stem Cell Transplantation / Q000379:methods
chemical_list: D004272:DNA, Mitochondrial
keywords: gene therapies; mitochondrial disorders; pharmaceuticals; protein; treatment