Генная терапия нейродегенеративных заболеваний: достижения, разработки, проблемы внедрения в клиническую практику

Нейродегенеративные заболевания (НДЗ) являются одними из перспективных объектов для разработки препаратов генной терапии, в первую очередь ввиду возможной причины их возникновения (нарушение работы гена или генов), отсутствия эффективной терапии, негативного влияния на качество жизни как самого пациента, так и его окружения.

Цель работы — анализ направлений и проблем разработки, проведения доклинических и клинических исследований препаратов генной терапии для лечения нейродегенеративных заболеваний, а также изучение зарубежного опыта экспертной оценки регистрационного досье препарата Zolgensma®, получившего условную государственную регистрацию.

Анализ проводимых исследований продуктов генной терапии в области НДЗ показал, что основными проблемами являются: в исследованиях на животных — выбор модели заболевания, способа введения, подбор мишени для эффективной генной терапии при заболеваниях, затрагивающих работу нескольких генов; на этапе клинических исследований (КИ) — выбор группы сравнения, разработка критериев отбора пациентов для участия в КИ с учетом наличия генетической мутации, которая является показанием к проведению генной терапии, исключения из КИ пациентов при наличии у них антител к продукту генной терапии, выбор и обоснование безопасной терапевтической дозы вследствие единственного шанса у пациента на введение препарата генной терапии, сложность оценки клинической пользы по экспрессии трансгена в организме у человека вследствие недоступности тканей мозга для анализа. Прорывом последних лет является вывод на мировой фармацевтический рынок препарата генной терапии Zolgensma® (Novartis) для лечения детей со спинальной мышечной атрофией 1 типа. В статье проанализирован опыт экспертной оценки регистрационного досье препарата Zolgensma®, который может быть использован разработчиками в ходе вывода на рынок Евразийского экономического союза лекарственных препаратов по механизму условной регистрации, подразумевающей, что польза от немедленного доступа пациентов к препаратам будет превышать риски, связанные с неполными данными об их характеристиках.

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