Current and Emerging Clinical Treatment in Mitochondrial Disease

Abstract

Primary mitochondrial disease (PMD) is a group of complex genetic disorders that arise due to pathogenic variants in nuclear or mitochondrial genomes. Although PMD is one of the most prevalent inborn errors of metabolism, it often exhibits marked phenotypic variation and can therefore be difficult to recognise. Current treatment for PMD revolves around supportive and preventive approaches, with few disease-specific therapies available. However, over the last decade there has been considerable progress in our understanding of both the genetics and pathophysiology of PMD. This has resulted in the development of a plethora of new pharmacological and non-pharmacological therapies at varying stages of development. Many of these therapies are currently undergoing clinical trials. This review summarises the latest emerging therapies that may become mainstream treatment in the coming years. It is distinct from other recent reviews in the field by comprehensively addressing both pharmacological non-pharmacological therapy from both a bench and a bedside perspective. We highlight the current and developing therapeutic landscape in novel pharmacological treatment, dietary supplementation, exercise training, device use, mitochondrial donation, tissue replacement gene therapy, hypoxic therapy and mitochondrial base editing. Supplementary Information The online version contains supplementary material available at 10.1007/s40291-020-00510-6.

Mitochondrial Aminoacyl-tRNA Synthetase and Disease: The Yeast Contribution for Functional Analysis of Novel Variants

“…However, if a beneficial effect deriving from the supplementation of the substrate amino acid is observed in yeast, it is certainly worth to experiment amino acid supplementation in mt ARS -patients. In fact, substrate enhancement, which in some cases can be obtained through dietary supplementation, is an emerging treatment for mitochondrial pathologies [ 106 ].…”

Movement Disorders in Children with a Mitochondrial Disease: A Cross-Sectional Survey from the Nationwide Italian Collaborative Network of Mitochondrial Diseases

“…One additional limitation of our study, also connected to the retrospective nature, is the scarcity of data related to the use of standardized scales to assess the disease course of the movement disorder. Although there are not yet effective disease-modifying therapies, an increasing number of pharmacological clinical trials are being conducted in MDs [ 40 ]. The use of sensitive and valid endpoints is essential to prepare well-stratified clinical cohorts to test the effectiveness of potential treatments.…”

Epilepsy in Mitochondrial Diseases—Current State of Knowledge on Aetiology and Treatment

“…Most interventions and guidelines are related to symptomatic treatment, with supplementation of cofactors, vitamins, or antioxidants, and mild exercises are recommended. Despite numerous studies, the efficacy of most of these interventions has not been confirmed [ 39 , 40 , 41 , 42 , 43 ].…”