Neuromuscular DiseasesNeuromuscular DiseasesНервно-мышечные болезни2222-87212413-0443Publishing House ABV Press69810.17650/2222-8721-2026-16-1-36-49LECTURES AND REVIEWSЛЕКЦИИ И ОБЗОРЫReview ArticleCurrent and emerging approaches to the treatment of amyotrophic lateral sclerosisАктуальные и перспективные подходы к лечению бокового амиотрофического склерозаhttps://orcid.org/0009-0002-1334-9730ShevchukD. V.ШевчукД. В.
Russian Federation
dvlshev@gmail.comhttps://orcid.org/0000-0002-7960-1006AbramovaA. A.АбрамоваА. А.
Russian Federation
dvlshev@gmail.comhttps://orcid.org/0000-0002-1072-9968ZakharovaM. N.ЗахароваМ. Н.
Russian Federation
dvlshev@gmail.comRussian Center of Neurology and NeurosciencesФГБНУ «Российский центр неврологии и нейронаук»2306202616136492206202622062026Copyright ©; 2026, ABV-PressCopyright ©; 2026, АБВ-пресс2026ABV-PressАБВ-прессhttps://nmb.abvpress.ru/jour/about/editorialPolicieshttps://nmb.abvpress.ru/jour/article/view/698

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the degeneration of both upper and lower motor neurons, leading to progressive muscle weakness, skeletal muscle atrophy, and eventual respiratory failure. Despite significant advances in understanding the molecular mechanisms underlying the disease, effective pathogenetic treatments remain limited. This review summarizes current data on pharmacological and experimental approaches to ALS therapy. We discuss the mechanisms of action and clinical efficacy of approved drugs, including riluzole and edaravone, as well as the targeted genetic therapy tofersen, developed for patients with mutations in the SOD1 gene. Special attention is given to the combination of sodium phenylbutyrate and taurursodiol (AMX0035), which was initially approved based on the results of the CENTAUR trial but was subsequently voluntarily withdrawn following negative results from the confirmatory phase III trial (PHOENIX). Furthermore, we analyze promising therapeutic avenues currently at various stages of clinical investigation. These include anti-inflammatory and immunomodulatory agents, mitochondrial neuroprotectants, cell-based technologies, and targeted genetic strategies such as antisense oligonucleotides and gene therapy. It is emphasized that current therapeutic interventions only provide a moderate slowing of disease progression, a limitation attributed to the pronounced pathogenetic heterogeneity of ALS and its late diagnosis. Consequently, future progress in treating ALS is expected to hinge on earlier disease detection, the implementation of molecular biomarkers, and the development of personalized, combination treatment strategies targeting the various components of its pathogenesis.

Боковой амиотрофический склероз (БАС) – прогрессирующее нейродегенеративное заболевание, в основе которого лежит поражение центральных и периферических мотонейронов, приводящее к прогрессирующей слабости и атрофии скелетных мышц и дыхательной недостаточности. Несмотря на значительный прогресс в изучении молекулярных механизмов заболевания, эффективные патогенетические методы лечения остаются ограниченными. В обзоре обобщены современные данные о фармакологических и экспериментальных подходах к терапии БАС. Рассматриваются механизмы действия и клиническая эффективность одобренных препаратов, включая рилузол и эдаравон, а также генетической таргетной терапии тоферсеном, предназначенной для пациентов с мутациями в гене SOD1. Отдельное внимание уделено комбинации натрия фенилбутирата и таурурсодиола (AMX0035), первоначально одобренной на основании результатов исследования CENTAUR, но впоследствии добровольно отозванной после отрицательных результатов подтверждающего исследования фазы III (PHOENIX). Анализируются перспективные направления терапии, находящиеся на разных этапах исследований, включая противовоспалительные и иммуномодулирующие препараты, митохондриальные нейропротекторы, клеточные технологии, а также генетические таргетные стратегии, такие как антисмысловые олигонуклеотиды и генная терапия. Подчеркивается, что существующие терапевтические вмешательства обеспечивают лишь умеренное замедление прогрессирования заболевания, что связано с выраженной патогенетической гетерогенностью БАС и поздней диагностикой. Прогресс в лечении БАС связывают с более ранним выявлением болезни, внедрением молекулярных биомаркеров и разработкой персонализированных комбинированных стратегий лечения, направленных на разные звенья патогенеза.

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