Abstract
Mitochondrial diseases are a clinically and genetically heterogeneous group of disorders that result from dysfunction of the mitochondrial oxidative phosphorylation due to molecular defects in genes encoding mitochondrial proteins. Despite the advances in molecular and biochemical methodologies leading to better understanding of the etiology and mechanism of these diseases, there are still no satisfactory therapies available for mitochondrial disorders. Treatment for mitochondrial diseases remains largely symptomatic and does not significantly alter the course of the disease. Based on limited number of clinical trials, several agents aiming at enhancing mitochondrial function or treating the consequences of mitochondrial dysfunction have been used. Several agents are currently being evaluated for mitochondrial diseases. Therapeutic strategies for mitochondrial diseases include the use of agents enhancing electron transfer chain function (coenzyme Q10, idebenone, riboflavin, dichloroacetate, and thiamine), agents acting as energy buffer (creatine), antioxidants (vitamin C, vitamin E, lipoic acid, cysteine donors, and EPI-743), amino acids restoring nitric oxide production (arginine and citrulline), cardiolipin protector (elamipretide), agents enhancing mitochondrial biogenesis (bezafibrate, epicatechin, and RTA 408), nucleotide bypass therapy, liver transplantation, and gene therapy. Although, there is a lack of curative therapies for mitochondrial disorders at the current time, the increased number of clinical research evaluating agents that target different aspects of mitochondrial dysfunction is promising and is expected to generate more therapeutic options for these diseases in the future.
•There are still no satisfactory therapies available for mitochondrial disorders.•Several agents are currently used and being evaluated for mitochondrial diseases.•Agents enhancing electron transfer chain function or mitochondrial biogenesis are used in mitochondrial diseases.•Energy buffer, antioxidants, and cardiolipin protector are also used in mitochondrial diseases.•Role of liver transplantation and gene therapy in treating mitochondrial diseases are also discussed.•An increased number of clinical research evaluates agents targeting different aspects of mitochondrial dysfunction.