Возможности и перспективы доклинической оценки лекарственной безопасности с использованием альтернативных методов: опыт реализации программы «Токсикология в XXI веке» в США

Актуальность. Консорциумом Tox21 (США) разработана и успешно реализуется «Программа по токсикологии в XXI веке», направленная на переход к новой стратегии, согласно которой изучение токсичности химических веществ на животных будет заменено широким спектром подходов, базирующихся на тестах in vitro и вычислительных методах.

Цель. Обзор информации об альтернативных моделях in vitro, разработанных для изучения токсичности химических соединений в рамках программы «Токсикология в XXI веке».

Обсуждение. Анализ информации, представленной Национальной токсикологической программой США (National Toxicology Program), Агентством по охране окружающей среды США (Environmental Protection Agency), Национальным центром развития трансляционных наук (National Center for Advancing Translational Sciences) и другими участниками консорциума Tox21 на официальных сайтах и в научной литературе, показал, что к настоящему времени разработана технология высокопроизводительного скрининга для тестирования безопасности химических веществ. С использованием этой технологии сформирована библиотека химических соединений Tox21 10К. Находящаяся в ней информация успешно используется для создания моделей, позволяющих прогнозировать токсичность химических веществ до начала доклинических исследований. Предложены новые подходы к изучению безопасности соединений на клеточных линиях человека для замены in vivo исследований. Создание моделей с использованием органов-на-чипах, мультиорганов-на-чипах и органоидов позволит преодолеть недостатки и ограничения применения моделей на основе клеточных линий и обеспечить более точное воспроизведение сложных взаимодействий клеток и матрикса, а также органов между собой. Новые технологии транскриптомики (токсикогеномики), разработанные в ходе реализации программы Tox21 для выявления новых биомаркеров и генных сигнатур токсичности химических веществ, могут быть применены для классификации токсикантов в соответствии со степенью риска для здоровья и выявления потенциальных побочных эффектов задолго до того, как будут обнаружены какие-либо патологические изменения в организме. Межведомственный координационный комитет по валидации альтернативных методов (Interagency Coordinating Committee on the Validation of Alternative Methods) проводит техническую оценку альтернативных методов испытаний и способствует их внедрению в регуляторную практику.

Выводы. Разработанные в рамках программы Тох21 новые подходы к изучению токсичности позволят осуществить переход от тестирования потенциальных лекарственных средств in vivo к компьютерным и in vitro методам, обеспеченным новыми инструментами и технологиями.

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