Mitochondrial disease in adults: recent advances and future promise.

Mitochondrial diseases are some of the most common inherited neurometabolic disorders, and major progress has been made in our understanding, diagnosis, and treatment of these conditions in the past 5 years. Development of national mitochondrial disease cohorts and international collaborations has changed our knowledge of the spectrum of clinical phenotypes and natural history of mitochondrial diseases. Advances in high-throughput sequencing technologies have altered the diagnostic algorithm for mitochondrial diseases by increasingly using a genetics-first approach, with more than 350 disease-causing genes identified to date. While the current management strategy for mitochondrial disease focuses on surveillance for multisystem involvement and effective symptomatic treatment, new endeavours are underway to find better treatments, including repurposing current drugs, use of novel small molecules, and gene therapies. Developments made in reproductive technology offer women the opportunity to prevent transmission of DNA-related mitochondrial disease to their children.
Competing Interests: Declaration of interests GSG reports grants from the Wellcome Trust, the UK Medical Research Council (MRC), and Lily Foundation, during the conduct of the study; and grants from Stealth Therapeutics, Reneo, Julius Clinical (Khondrion), Neurovive, and AMO Pharma, outside the submitted work. TK reports grants and personal fees from Santhera Pharmaceuticals and Chiesi GmbH; and grants from Gensight Biologics and Stealth Biotherapeutics, outside the submitted work. CK reports personal fees from Santhera, Sanofi Genzyme, Hormosan, Novartis, and Roche; and personal fees and other from Stealth Biotherapeutics, outside the submitted work. RM reports grants from Wellcome and the MRC, during the conduct of the study; consultancy fees from Minovia Therapeutics and Reneo to the institution; and personal fees from Eisai, outside the submitted work. AS reports grants from the Jane and Aatos Erkko Foundation and Business Finland; and personal fees from Khondrion, outside the submitted work; AS also has a patent pending for NAD concentration measurement and a patent pending for multibiomarkers for mitochondrial disease. RWT reports grants from the Wellcome Trust, the MRC, and the Lily Foundation, during the conduct of the study. DRT reports grants from the Australian National Health and Medical Research Council (NHMRC) and the US Department of Defense, during the conduct of the study. DMT reports grants from the Wellcome Trust, the MRC, and the National Institute for Health Research (NIHR); and personal fees from Khondrion, Imel, Pretzel therapeutics, and Nanna therapeutics, outside the submitted work. All other authors declare no competing interests.
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