Treatment of mitochondrial diseases

To date, effective treatment of mitochondrial diseases remains an unresolved problem. This is due to several factors: the difficulties of early diagnosis, the poor knowledge of individual links in the pathogenesis of diseases, the rarity of some forms of pathology, the severity of the condition of patients due to the multisystemic nature of the lesion, making it difficult to assess the treatment being conducted, and the lack of a unified view of the effectiveness of therapy. Ways of drug correction are based on the knowledge gained on the pathogenesis of individual forms of mitochondrial diseases.

The pathogenesis of mitochondrial diseases caused by defects in the respiratory chain is mainly due to a deficiency of enzyme complexes, a violation of structural and transport proteins of the mitochondria. This leads to a deep breakdown of the entire system of tissue respiration, the accumulation of under-oxidized metabolic products, lactate acidosis, the disruption of lipid peroxidation, the deficiency of carnitine, coenzyme Q-10, etc. In this regard, the main therapeutic measures are aimed at optimizing the processes of biological oxidation and tissue respiration and correction of the deficit of individual metabolites, which develops in mitochondrial dysfunctions.

Complex treatment of patients with these pathologies is currently based on the following principles:

• restriction of easily digestible carbohydrates in the diet of patients (up to 10 g / kg body weight);
• use of correctors for active electron transfer in the respiratory chain;
• the introduction of cofactors of enzyme reactions that occur in cells;
• prevention of progression of mitochondrial damage;
• elimination of lactic acidosis:
• elimination of carnitine deficiency;
• the appointment of antioxidants;
• the use of symptomatic means;
• prevention of secondary mitochondrial dysfunctions.

The complex of medicines designed to correct mitochondrial disorders includes mainly 4 groups of drugs:

• 1 st group - means aimed at activation of the transfer of electrons in the respiratory chain:
  • coenzyme Q-10 * - 30-60 mg / day for 2 months (4-5 mg / kg per day in 2 doses);
  • kudesan - 30-150 mg / day (course - 2 months) 2-3 courses per year. The maintenance dose is 15-30 mg / day (in a 20 ml bottle, 1 ml contains 30 mg of coenzyme Q-10 and 4.5 mg of vitamin E);
  • succinic acid - 8-10 mg / kg daily for 2 months (3 days reception, 2 days break), up to 6 g / day with deficiency of respiratory complex 1 and deficiency of pyruvate dehydrogenase complex.
• 2 nd group - means cofactor therapy (average duration of the course - 1 month):
  • nicotinamide - 20-30 mg / day;
  • riboflavin - 20-30 mg / day (3-20 mg / kg per day in 4 sessions);
  • thiamin - 20-30 mg / day (25-100 mg / kg per day);
  • thioctic acid - 100-200 mg / day (5-50 mg / day);
  • biotin - 5 mg / day (in severe cases up to 20 mg / day).
• 3-rd group - correctors of the broken metabolism of fatty acids;
  • 20% solution of levocarnitine - 30-50 mg / kg per day for 3-4 months (taken before meals, diluted with liquid, 1 tsp corresponds to 1.0);
  • Levokarnitin - 25-100 mg / kg per day in 4 sessions.
• 4-th group - means aimed at preventing oxygen-radical damage to mitochondrial membranes (3-4 weeks):
  • ascorbic acid - 200-500 mg / day;
  • vitamin E - 50-300 mg / day.

For the correction of lactic acidosis, dimephosphon 30 mg / kg (1 month), dichloroacetate 15 mg / kg per day for 3 doses (increased risk of developing neuropathy with long-term administration due to thiamine deficiency) or 2-chloropropionate.

If necessary, use the methods of symptomatic treatment: IVL, blood transfusion, peritoneal dialysis, etc.

Persons with mitochondrial diseases should avoid prolonged interruptions in food intake, carbohydrate load. A ketogenic diet is prescribed for a defect of pyruvate dehydrogenase and a complex 1 defect. Excessive physical exertion should also be avoided. It is necessary to treat associated infections. It is important to remember the negative impact on the functioning of bioenergetic systems of a number of medications (barbiturates, preparations of valproic acid, chloramphenicol, tetracycline, etc.), which should be administered individually. In the presence of a convulsive syndrome, anticonvulsants (valproic acid preparations at 30 mg / kg daily, clonazepam, etc.) are shown, but their negative side effect on mitochondrial functions should be taken into account.

The duration of the course of treatment ranges from 2 to 4 months, it is repeated 2-3 times a year.