Neuromuscular DiseasesNeuromuscular DiseasesНервно-мышечные болезни2222-87212413-0443Publishing House ABV Press67110.17650/2222-8721-2025-15-3-38-46LECTURES AND REVIEWSЛЕКЦИИ И ОБЗОРЫReview ArticleTargets of epigenetic regulation in Duchenne muscular dystrophy: pathogenetic and clinical background for myoprotective anti-inflammatory and antifibrotic therapyМишени эпигенетической регуляции при прогрессирующей мышечной дистрофии Дюшенна: патогенетическая и клиническая целесообразность применения миопротективной противовоспалительной и антифиброзной терапииhttps://orcid.org/0000-0003-2635-2752VlodavetsDmitriy V.ВлодавецДмитрий Владимирович
Russian Federation

Y. E. Veltishev Research and Clinical Institute for Pediatrics

Научно-исследовательский клинический институт педиатрии и детской хирургии им. акад. Ю.Е. Вельтищева

mityaus@gmail.comN. I. Pirogov Russian National Research Medical University, Ministry of Health of RussiaФГАОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России2412202515338462012202520122025Copyright ©; 2025, Vlodavets D.V.Copyright ©; 2025, Влодавец Д.В.2025Vlodavets D.V.Влодавец Д.В.https://creativecommons.org/licenses/by/4.0https://nmb.abvpress.ru/jour/article/view/671

Duchenne muscular dystrophy is an inherited X-linked disorder characterized by progressive muscle wasting, loss of mobility, and death from cardiorespiratory complications. The absence of functional dystrophin triggers a cascade of pathological events in muscles including chronic inflammation, impaired regeneration, and substitutive fibroadipose degeneration. New approaches aimed at restoring or replacing dystrophin synthesis increased the delay in loss of ambulation achieved with standard corticosteroid therapy, but high demand for a different mechanism of action regardless of the DMD mutation variant remains. Givinostat is the first histone deacetylase inhibitor for Duchenne muscular dystrophy treatment, showing a positive myoprotective effect on key pathogenetic consequences of dystrophin dysfunction regardless of the mutation in the DMD gene. In clinical studies, givinostat improves motor function, reduces inflammatory infiltration and fibroadipose degeneration of muscle tissue, and allows to delay the loss of ambulatory function by almost 3 years.

Прогрессирующая мышечная дистрофия Дюшенна – наследственное Х-сцепленное заболевание, характеризующееся прогредиентным ослаблением мускулатуры, потерей способности к самостоятельному передвижению и гибелью от кардиореспираторных осложнений. Отсутствие функционального белка дистрофина при прогрессирующей мышечной дистрофии Дюшенна опосредованно запускает каскад патологических событий, включающий хроническое воспаление, нарушение регенерации и заместительную фиброзно-жировую дистрофию. Подходы, направленные на восстановление или замещение синтеза дистрофина, позволили увеличить отсрочку потери амбулаторности, достигнутую стандартной терапией глюкокортикостероидами, однако сохраняется высокая потребность в терапии с отличным механизмом действия вне зависимости от варианта мутации в гене DMD. Гивиностат – первый ингибитор гистондеацетилазы для лечения прогрессирующей мышечной дистрофии Дюшенна, оказывающий положительный миопротективный эффект на ключевые патогенетические последствия дисфункции дистрофина вне зависимости от мутации в гене DMD. По данным клинических исследований, применение гивиностата улучшает моторную функцию, снижает воспалительную инфильтрацию и фиброзно-жировую дегенерацию мышечной ткани, а также позволяет отсрочить потерю амбулаторности почти на 3 года.

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