Дифференцированный подход к фармакотерапии расстройств аутистического спектра: биохимические аспекты

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Аннотация

Расстройства аутистического спектра (РАС) - это высоко гетерогенные нейроонтогенетические заболевания, вызываемые сложным взаимодействием многочисленных генетических факторов и факторов внешней среды, приводящим к нарушениям формирования нервной системы на ранних этапах развития. В настоящее время отсутствуют общепринятые фармакологические методы лечения нарушений социальной коммуникации и ограниченных и повторяющихся моделей поведения, так называемых ядерных симптомов РАС. В качестве причин неудач клинических испытаний фармакотерапии РАС рассматриваются, в частности, недостаток знаний о биологических основах РАС, отсутствие клинически значимых биохимических параметров, отражающих нарушение сигнальных молекулярных каскадов, управляющих развитием и функционированием нервной системы, и отсутствие методов выделения гомогенных по клиническим и биологическим показателям подгрупп больных. В настоящем обзоре рассмотрены возможности применения дифференцированного клинико-биологического подхода к целевому поиску фармакотерапии РАС с акцентом на биохимические маркеры, связанные с РАС, и попытки стратификации пациентов по биохимическим показателям. Обсуждается использование подхода «мишень-ориентированная терапия и оценка состояния мишени до лечения и в процессе лечения для возможного выделения больных с положительным ответом на лечение» на примере опубликованных результатов клинических испытаний. Сделан вывод о том, что выявление биохимических показателей для выделения подгрупп больных РАС требует проведения исследований на больших выборках, отражающих клиническое и биологическое разнообразие больных с РАС, и использования единых подходов для проведения подобных исследований. Комплексный подход, включающий клинические наблюдения, клинико-психологическую оценку поведения пациентов, изучение анамнеза и составление индивидуальных молекулярных профилей, должен стать новой стратегией для стратификации и выделения подгрупп пациентов с РАС для клинических испытаний фармакотерапии, а также для оценки её эффективности.

Об авторах

И. С Бокша

ФГБНУ «Научный центр психического здоровья»

Email: boksha_irina@mail.ru
115522 Москва, Россия

Т. А Прохорова

ФГБНУ «Научный центр психического здоровья»

Email: boksha_irina@mail.ru
115522 Москва, Россия

О. К Савушкина

ФГБНУ «Научный центр психического здоровья»

Email: boksha_irina@mail.ru
115522 Москва, Россия

Е. Б Терешкина

ФГБНУ «Научный центр психического здоровья»

Email: boksha_irina@mail.ru
115522 Москва, Россия

Г. Ш Бурбаева

ФГБНУ «Научный центр психического здоровья»

Email: boksha_irina@mail.ru
115522 Москва, Россия

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