Therapy of Spinal Muscular Atrophy at the Present Stage: a Review

INTRODUCTION. Spinal muscular atrophy (SMA) is a group of hereditary neuromuscular diseases that primarily affect infants and children. It is caused by a mutation in the gene encoding the survival motor neuron protein, leading to the degeneration of motor neurons and resulting in paralysis, muscle atrophy, and, in severe cases, death within the first two years of life. Currently, the course of the disease has been changed due to the development of special drugs. Three drugs have been approved for the treatment of spinal muscular atrophy: nusinersen, onasemnogene abeparvovec and risdiplam, which have shown clear positive results. AIM. Conduct an analysis of publications devoted to the history of development, implementation into clinical practice and evaluation of the effectiveness of modern drugs for the treatment of spinal muscular atrophy. MATERIALS AND METHODS. Based on the primary identification of 64 articles presented in domestic and foreign databases (PubMed, Cochrane Library, Cyberleninka.ru) for the period 1998-2024, 33 scientific publications were selected. RESULTS AND DISCUSSION. Nusinersen is an antisense oligonucleotide administered intrathecally. Its mechanism of action is modification of SMN2 pre-mRNA splicing. The recommended dosing regimen is four loading doses of 12 mg, followed by maintenance doses every 4 months. It is intended for the treatment of patients with spinal muscular atrophy from birth. . It is administered intrathecally three or four times during the loading period and every four or six months during the maintenance period The efficacy of treatment with the drug is higher in asymptomatic patients. Onasemnogene abeparvovec is a scAAV9-SMN-based drug, an adeno-associated viral vector, which is administered intravenously. Its mechanism of action is transfer of the SMN gene. It is used for patients with all forms and types of spinal muscular atrophy who are under 2 years of age (and weigh no more than 13.5 kg) at the time of drug administration. It is administered as a single intravenous infusion, which takes 1 hour. Risdiplam is an oral solution that alters the splicing of SMN2 pre-mRNA, promoting the inclusion of exon 7 and increasing levels of functional SMN protein. It allows patients with spinal muscular atrophy to receive treatment in the comfort of their own home. It is taken once daily, with the dosage depending on age and body weight. Adults and children > 2 years and weighing ≥ 20 kg take 5 mg risdiplam once daily. For children ≥ 2 years and weighing < 20 kg, the dose is calculated based on body weight (usually 0.25 mg/kg once daily). CONCLUSION. With the introduction of new drugs into clinical practice, the timing and accuracy of diagnosis of spinal muscular atrophy have become more important than ever before. Nusinersen, onasemnogene abeparvovec and risdiplam, which have shown clear positive results, are more effective in asymptomatic patients, which highlights the importance of early detection of the disease (newborn screening). If treatment cannot be initiated at the appropriate time due to late diagnosis or misdiagnosis, therapeutic efficacy may be significantly reduced. Treatment of patients with developed symptoms of spinal muscular atrophy requires further research in this area.