Josef Finsterer. Clinical therapeutic management of human mitochondrial disorders. Pediatric Neurology. Article in press’
Despite recent advances in the elucidation of etiology and pathogenesis of mitochondrial disorders (MIDs), their therapeutic management remains challenging. This review focuses on currently available therapeutic options for human MIDs.
Current treatment of MIDs relies on symptomatic, multidisciplinary therapies of various manifestations in organs such as the brain, muscle, nerves, eyes, ears, endocrine organs, heart, intestines, kidneys, lungs, bones, bone-marrow, cartilage, immune-system, and skin. If respiratory-chain functions are primarily or secondarily impaired, antioxidants or cofactors should be additionally given one-by-one. To all MID patients an individually-tailored diet and physical training-program should be offered. Irrespective of the pathogenesis, all MID patients should avoid exposure to mitochondrion-toxic agents and environments. Specific treatment can be offered for stroke-like episodes, mitochondrial epilepsy, mitochondrial neuro-gastro-intestinal encephalopathy (MNGIE), Leber’s hereditary optic neuropathy (LHON), thiamine-responsive Leigh syndrome, primary coenzyme-Q-deficiency, primary carnitine-deficiency, Friedreich ataxia, ethylmalonic encephalopathy, acyl-CoA-dehydrogenase-deficiency, pyruvate-dehydrogenase deficiency, and hereditary vitamin-E-deficiency. Preventing the transmission of mtDNA-related MIDs can be achieved by mitochondrion-replacement therapy (spindle transfer, pronuclear transfer).
In conclusion, specific and non-specific therapies for human MIDs are available and beneficial effects have been anecdotally reported. However, double-blind, placebo-controlled studies to confirm effectivity are lacking for the majority of the measures applied to MIDs. Transmission of certain MIDs can be prevented by mitochondrion-replacement therapy. A multidisciplinary approach is required to meet the therapeutic challenges of MID patients.