Current Options in the Treatment of Mitochondrial Diseases

Abstract

Mitochondrial diseases (MD) are disorders caused by an impairment of the mitochondrial respiratory chain function. They are usually progressive, isolated or multi-system diseases and have variable times of onset. Because mitochondria have their own DNA (mtDNA), MD can be caused by mutations in both mtDNA and nuclear DNA (nDNA). The complexity of genetic control of mitochondrial function is in part responsible for the intra- and inter-familiar clinical heterogeneity of this class of diseases. Despite the remarkable progress in understanding of the molecular bases of these disorders, therapy of MD is quite inadequate. Present options of treatment mainly include physical, pharmacological and gene therapy approaches. Aerobic exercise and physical therapy is useful to prevent or correct deconditioning and may improve exercise tolerance. Pharmacological approach is based on removing noxious metabolites, using reactive oxygen species scavengers and administrating vitamins and cofactors which is especially important in case of primary deficiencies of specific compounds such as Coenzyme Q10. Gene therapy is fascinating but it is difficult to apply because of polyplasmy and heteroplasmy. Experimental methods include gene shifting, allotopic expression, mitochondrial transfection or correcting mtDNA mutations with specific restriction endonucleases. Here, we discussed some recent patents. Progresses in each of these fields may open interesting perspectives for the future.

Mutation in cytochrome b gene of mitochondrial DNA in a family with fibromyalgia is associated with NLRP3-inflammasome activation

“…Interestingly, it has been reported that CoQ 10 inhibits NLRP3-inflammasome activation in patients with FM 12. Furthermore, MitoQ, a mitochondria-targeted derivative of CoQ 10 , has also been reported to inhibit NLRP3-inflammasome 54. As CoQ 10 is a common treatment for mitochondrial diseases,30–32 55 56 here, we report another potential mechanism by which CoQ 10 treatment can be effective in these patients.…”

Angiotensin II type 1 receptor blockers increase tolerance of cells to copper and cisplatin

“…This is of particular importance as mitochondrial dysfunction, ROS and apoptosis have been linked to several human conditions such as aging, cancer 100, diabetes 101102 and non-alcoholic steatohepatitis 103, but also neurodegenerative disorders 104 including Alzheimer disease 105 and Parkinson’s disease 106107, and rare diseases such as WD 4. Current treatment options for mitochondrial dysfunction-related disorders are inadequate and mostly consist of the administration of cofactors and oxygen radical scavengers 108109110. Thus, there still is an urgent need for novel treatments in combating mitochondrial dysfunction-related disorders and ARBs may show promise, as well as OSIP108, in this regard.…”

Neurodegenerative and Fatiguing Illnesses, Infections and Mitochondrial Dysfunction: Use of Natural Supplements to Improve Mitochondrial Function.

“…They are essential in the support of mitochondrial function by providing antioxidants, cofactors, metal ions, salts, and other molecules that are essential in supporting the functions of mitochondrial enzymes, electron transport systems, mtDNA replication, fat and sugar metabolism, protein synthesis and proper antioxidant balance [296][297][298]. Vitamins, such as B (multiple), D, E, C, and ions, such as iron, magnesium, manganese, zinc, among other small molecules, are important n this regard, and up to one-half of the aging North American population is deficient in these vitamins, minerals and other micronutrients [299].…”

“…The use of micronutrients in helping to restore and/or maintain mitochondrial function has proven useful in consert with other treatment modialties [296,298,300]. Although there are few clinical trials in the literature that demonstrate the usefulness and utility of supplementation with only vitamins, minerals, antioxidants and other micronutrients alone in supporting mitochondrial function, the ones that have been conducted clearly show the importance of providing adequate oral doses of vitamins, minerals, antioxidants and other micronutrients to maintain mitochondrial energy functions [296.…”