perinatologyРоссийский вестник перинатологии и педиатрииRossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics)1027-40652500-2228Ltd. “The National Academy of Pediatric Science and Innovation”10.21508/1027-4065-2016-61-5-106-112perinatology-390Research ArticleВ ПОМОЩЬ ПРАКТИЧЕСКОМУ ВРАЧУFOR THE PRACTITIONERТаргетная терапия туберозного склерозаTargeted therapy for tuberous sclerosis complexБелоусоваЕ. Д.BelousovaE. D.

отдел психоневрологии и эпилептологии 

д.м.н., проф., зав. отделом 

ВлодавецД. В.VlodavetsD. V.

отдел психоневрологии и эпилептологии 

к.м.н., ст. н. сотр. отдела 

mityaus@gmail.comПивовароваА. М.PivovarovaA. M.

отдел организации и развития научно-исследовательской и инновационной деятельности 

к.м.н., ст. н. сотр. 

КатышеваО. В.KatyshevaO. V.

отделение нефрологии 

врач

ДорофееваМ. Ю.DorofeevaM. Yu.

к.м.н., вед. н. сотр. отдела

ОСП «Научно-исследовательский клинический институт педиатрии имени академика Ю.Е. Вельтищева» ГБОУ ВПО РНИМУ им. Н.И. Пирогова Минздрава РФ, МоскваРоссияAcademician Yu.E. Veltishchev Research Clinical Institute of Pediatrics, N.I. Pirogov Russian National Research Medical University, Ministry of Health of the Russian Federation, MoscowRussian Federation201620112016615106112Copyright © Ltd. “The National Academy of Pediatric Science and Innovation”, 20162016Ltd. “The National Academy of Pediatric Science and Innovation”Ltd. “The National Academy of Pediatric Science and Innovation”https://www.ped-perinatology.ru/jour/about/submissions#copyrightNoticehttps://www.ped-perinatology.ru/jour/article/view/390

Гены туберозного склероза (TSC1 и TSC2) в норме функционируют как классические гены-супрессоры опухолевого роста; потеря функции этих генов приводит к активации киназы mTOR и развитию доброкачественных опухолей. Несмотря на медленное прогрессирование, субэпендимальные гигантоклеточные астроцитомы и ангиомиолипомы почек могут вызывать летальные исходы. Ингибитор mTOR эверолимус продемонстрировал хорошую эффективность и переносимость как в I–II, так и в III фазе исследований (EXIST-1 и EXIST-2): уменьшение объема астроцитом на 50% и более — у 35% пациентов, объема ангиомиолипом на 50% и более — у 41,8%. Через 3,5 года исследований эверолимус демонстрировал высокий процент удержания на препарате — 80,2 и 79% соответственно. Побочные эффекты отмечались практически у всех пациентов, наиболее часто наблюдались стоматиты, язвы слизистой рта, назофарингит. Эверолимус был зарегистрирован в РФ, и рос- сийские пациенты принимали участие в международных исследованиях EXIST-1 и EXIST-2. Показания для назначения препарата при туберозном склерозе — субэпендимальные гигантоклеточные астроцитомы у пациентов старше 3 лет и ангиомиолипомы у пациентов старше 18 лет, ассоциированные с туберозным склерозом. Эверолимус обладает потенциалом таргетного воздействия на спектр клинических проявлений туберозного склероза. 

The tuberous sclerosis complex genes (TSC1 and TSC2) function as classic tumor suppressor genes in health; a loss of function of these genes results in activation of the kinase m-TOR and to development of benign tumors. Despite their slow progression, renal subependymal giant cell astrocytomas and angiomyolipomas can cause fatal outcomes. Both Phases I–II and III EXIST-1 and EXIST-2 trials demonstrated that the m-TOR inhibitor everolimus had good efficacy and tolerability: the volume of astrocytomas and that of angomyolipomas were reduced by 50% or more in 35 and 41% of patients, respectively. After 3.5 years of the trials, everolimus showed a high retention rate: 80.2 and 79% of the patients, respectively. Virtually all patients were observed to have adverse reactions, most commonly stomatitis, oral ulcers, and nasopharyngitis. Everolimus has been registered in the Russian Federation and Russian patients participated in the EXIST-1 and EXIST-2 trials. The indications for prescribing the drug are tuberous sclerosis complex-associated subependymal giant cell astrocytomas and angomyolipomas in patients older than 3 and in those older than 18 years of age, respectively. Everolimus has the potential for targeted treatment for the spectrum of clinical manifestations of tuberous sclerosis complex. 

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The authors declare that there are no conflicts of interest present.