Current progress in the therapeutic options for mitochondrial disorders.

Abstract

Mitochondrial disorders manifest enormous genetic and clinical heterogeneity - they can appear at any age, present with various phenotypes affecting any organ, and display any mode of inheritance. What mitochondrial diseases do have in common, is impairment of respiratory chain activity, which is responsible for more than 90% of energy production within cells. While diagnostics of mitochondrial disorders has been accelerated by introducing Next-Generation Sequencing techniques in recent years, the treatment options are still very limited. For many patients only a supportive or symptomatic therapy is available at the moment. However, decades of basic and preclinical research have uncovered potential target points and numerous compounds or interventions are now subjects of clinical trials. In this review, we focus on current and emerging therapeutic approaches towards the treatment of mitochondrial disorders. We focus on small compounds, metabolic interference, such as endurance training or ketogenic diet and also on genomic approaches.

Cornstarch protocol for nocturnal hypoglycemia in adult patient with mitochondrial disorder

“…The approach to non-diabetic hypoglycemia in MTDs should initially focus on ruling out alternative causes, such as infections, autoimmune hypoglycemia, medication side effects, or insulinomas. MTDs have been associated with adrenal insu ciency which should also be considered in the evaluation [2].…”

“…Mitochondrial disorders (MTDs) are a group of rare, highly heterogeneous disorders most commonly involving genetic defects in the oxidation-phosphorylation pathway, which produces adenosine triphosphate [1]. As a group, they are among the most common forms of inborn errors of metabolism and inherited neurological disorders [2]. Presentation often includes multi-system characteristics and vary widely based on the hundreds of possible genetic mutations in mitochondrial or nuclear DNA, as well as the varying tissue distribution of affected mitochondria.…”

“…Presentation often includes multi-system characteristics and vary widely based on the hundreds of possible genetic mutations in mitochondrial or nuclear DNA, as well as the varying tissue distribution of affected mitochondria. Tissues with high energy requirements, such as the brain, retina, kidney, liver, and skeletal or cardiac muscle, are most commonly impacted [2]. Therefore, MTDs can be classi ed as metabolic myopathies.…”

“…The classi cation of metabolic myopathies also includes genetic defects in glycogenolysis, glycolysis, lipid metabolism, and purine metabolism [5]. In addition to oxidative-phosphorylation, mitochondria are involved with many metabolic processes such as gluconeogenesis, ketogenesis, tricarboxylic acid cycle, urea cycle, amino acid metabolism, and lipid metabolism [2]. Although hypoglycemia in mitochondrial disorders is not well studied, glycogen storage disorders commonly present with hypoglycemia.…”

Genetic Complementation of ATP Synthase Deficiency Due to Dysfunction of TMEM70 Assembly Factor in Rat

“…While mitochondrial myopathies are devastating genetic diseases, there are almost no causal therapies available for patients [ 36 , 37 ]. In general, mitochondrial disorders may be approached by either pharmaceutic interventions, upregulating respective metabolic pathways, or by the means of classical gene therapy.…”