Neuromuscular DiseasesNeuromuscular DiseasesНервно-мышечные болезни2222-87212413-0443Publishing House ABV Press59010.17650/2222-8721-2024-14-1-51-62LECTURES AND REVIEWSЛЕКЦИИ И ОБЗОРЫStages of research and development of therapeutic approaches for Duchenne myodystrophy. Part I: the period before etiotropic approaches introductionИсторические этапы поиска и разработки терапевтических подходов при миодистрофии Дюшенна. Часть I: период до внедрения этиотропных подходовhttps://orcid.org/0000-0002-0096-4542Kochergin-NikitskiyK. S.Кочергин-НикитскийК. С.
Russian Federation

Konstantin Sergeevich Kochergin‑Nikitskiy

1 Moskvorechye St., Moscow 115522

Константин Сергеевич Кочергин‑Никитский

115522 Москва, ул. Москворечье, 1

KochNik.KS@gmail.comhttps://orcid.org/0000-0002-1558-3048SmirnikhinaS. A.СмирнихинаС. А.
Russian Federation

1 Moskvorechye St., Moscow 115522

115522 Москва, ул. Москворечье, 1

https://orcid.org/0000-0003-4962-6947LavrovA. V.ЛавровА. В.
Russian Federation

1 Moskvorechye St., Moscow 115522

115522 Москва, ул. Москворечье, 1

Research Centre for Medical GeneticsФГБНУ «Медико-генетический научный центр им. акад. Н.П. Бочкова»0103202414151620103202401032024Copyright ©; 2024, Kochergin-Nikitskiy K.S., Smirnikhina S.A., Lavrov A.V.Copyright ©; 2024, Кочергин-Никитский К.С., Смирнихина С.А., Лавров А.В.2024Kochergin-Nikitskiy K.S., Smirnikhina S.A., Lavrov A.V.Кочергин-Никитский К.С., Смирнихина С.А., Лавров А.В.https://creativecommons.org/licenses/by/4.0https://nmb.abvpress.ru/jour/article/view/590

Duchenne muscular dystrophy is one of the most common inherited muscular dystrophies. The cause of this disease with an X‑linked recessive type of inheritance is mutations of the DMD gene, leading to the absence of the dystrophin protein this gene encodes or its impaired function. Loss of dystrophin leads to severe degenerative processes in patients, especially in muscle tissue, with impaired muscle function, loss of ability to move independently, respiratory failure, cardiomyopathies, etc.

More than 160 years have passed since the work of Guillaume‑Benjamin‑Armand Duchenne in the 19th century. Despite the efforts of many researchers who have developed various therapeutic approaches designed to alleviate the condition of patients if not cure it, few of them have significantly changed the course of the disease. Different approaches related to specific therapy of ischemia and fibrosis in affected muscles, correction of hormonal regulation of muscle tissue growth, therapeutic methods aimed at preventing damaged myocytes from excessive accumulation of calcium ions, which enhance proteolytic processes, suppression of oxidative stress in muscles, etc. have not yet shown high effectiveness both independently and in combination with glucocorticoids. The introduction of corticosteroid drugs made it possible to slow down disease development, but the average survival still does not exceed 30–40 years and patients spend many of them in a wheelchair. At the same time, the patients’ quality of life can be additionally diminished due to the common corticosteroids’ side effects.

Мышечная дистрофия Дюшенна является одной из наиболее распространенных наследственных миодистрофий. Причиной данного заболевания с X‑сцепленным рецессивным типом наследования являются мутации гена DMD, приводящие к отсутствию кодируемого им белка дистрофина или нарушению его функции. Потеря дистрофина приводит к тяжелым дегенеративным процессам у пациентов, особенно в мышечных тканях; следствием этих процессов становятся нарушение функционирования мышц, утрата способности к самостоятельному перемещению, дыхательная недостаточность, кардиомиопатии и др.

Со времени работ Гийома Бенджамена Армана Дюшенна в XIX веке прошло более 160 лет. Несмотря на усилия множества исследователей, разрабатывавших различные терапевтические подходы, призванные если не излечить, то хотя бы облегчить состояние пациентов, немногие из них позволили значительно повлиять на заболевание. Подходы, связанные со специфической терапией ишемии и фиброза в пораженных мышцах, коррекцией гормональной регуляции роста мышечных тканей, методы, направленные на предотвращение избыточного накопления ионов кальция в миоцитах и усиление протеолитических процессов, подавление оксидативного стресса в мышцах и пр., до настоящего времени не показали высокой эффективности как самостоятельно, так и в сочетании с глюкокортикостероидами. Применение глюкокортикостероидных препаратов позволяет замедлить развитие заболевания, но средняя продолжительность жизни пациентов до сих пор не превышает 30–40 лет, большую часть из которых они проводят в инвалидном кресле, при этом качество жизни пациентов бывает дополнительно снижено из‑за регулярно развивающихся побочных эффектов.

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