Treatment of mitochondrial diseases

To date, effective treatment of mitochondrial diseases remains an unsolved problem. This is due to several factors: difficulties in early diagnosis, poor study of individual links in the pathogenesis of diseases, the rarity of some forms of pathology, the severity of the patient's condition due to the multisystemic nature of the lesion, which complicates the assessment of the treatment, and the lack of a unified view on the criteria for the effectiveness of therapy. The methods of drug correction are based on the achieved knowledge of the pathogenesis of individual forms of mitochondrial diseases.

The pathogenesis of mitochondrial diseases caused by respiratory chain defects is mainly associated with a deficiency of enzyme complexes, a disorder of the structural and transport proteins of mitochondria. This leads to a profound disorder of the entire tissue respiration system, accumulation of underoxidized metabolic products, lactic acidosis, a disorder of lipid peroxidation processes, a 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 correcting the deficiency of individual metabolites that develops with mitochondrial dysfunctions.

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

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

The complex of medicinal products aimed at correcting mitochondrial disorders includes mainly 4 groups of drugs:

• 1st group - agents aimed at activating 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. Maintenance dose - 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 per day for 2 months (3 days on, 2 days off), up to 6 g/day for respiratory complex 1 deficiency and pyruvate dehydrogenase complex deficiency.
• 2nd group - cofactor therapy agents (average course duration - 1 month):
  • nicotinamide - 20-30 mg/day;
  • riboflavin - 20-30 mg/day (3-20 mg/kg per day in 4 doses);
  • thiamine - 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).
• 3rd group - correctors of impaired fatty acid metabolism;
  • 20% solution of levocarnitine - 30-50 mg/kg per day for 3-4 months (take before meals, diluted with liquid, 1 teaspoon corresponds to 1.0);
  • levocarnitine - 25-100 mg/kg per day in 4 doses.
• Group 4 - drugs aimed at preventing oxygen-radical damage to mitochondrial membranes (taken for 3-4 weeks):
  • ascorbic acid - 200-500 mg/day;
  • Vitamin E - 50-300 mg/day.

To correct lactic acidosis, dimephosphone is used - 30 mg/kg (1 month), dichloroacetate - 15 mg/kg per day in 3 doses (the risk of developing neuropathy increases with prolonged use due to thiamine deficiency) or 2-chloropropionate.

If necessary, symptomatic treatment methods are used: artificial ventilation, blood transfusion, peritoneal dialysis, etc.

People with mitochondrial diseases should avoid long breaks in food intake and carbohydrate loading. A ketogenic diet is prescribed for pyruvate dehydrogenase deficiency and complex 1 deficiency. Excessive physical activity should also be avoided. It is necessary to treat associated infections. It is important to remember the negative impact of a number of medications (barbiturates, valproic acid preparations, chloramphenicol, tetracycline, etc.) on the functioning of bioenergetic systems, which should be prescribed individually. In the presence of convulsive syndrome, anticonvulsants are indicated (valproic acid preparations at 30 mg/kg per day, clonazepam, etc.), but their negative side effects on mitochondrial functions must be taken into account.

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