Основные направления по разработке и модификации препаратов для лечения гемофилии

Основным методом лечения гемофилии А и В является заместительная терапия с использованием препаратов, получаемых из плазмы доноров или посредством технологии рекомбинантных ДНК. Среди основных недостатков немодифицированных препаратов факторов VIII и IX (FVIII и FIX) следует выделить низкий период циркуляции препарата в организме больного и выработку антител (ингибиторов) к белку препарата, что существенно снижает их эффективность. Повышение эффективности и безопасности рекомбинантных препаратов достигается за счет удаления В-домена в молекуле FVIII, пегилирования или разработки препаратов на основе слитных белков (fusion proteins – слияние молекулы препарата с альбумином или Fc-фрагментом IgG). Данные модификации в первую очередь способствуют повышению стабильности молекулы действующего вещества, увеличению периода полувыведения и снижению иммуногенности рекомбинантных препаратов. Заместительная терапия традиционными препаратами больных гемофилией, у которых определяются антитела (ингибиторы) к препарату, не эффективна. Учитывая это, в последние годы были разработаны новые препараты для альтернативных подходов методов лечения гемофилии. Разработан препарат на основе биспецифичных моноклональных антител, имитирующий функцию FVIII; моноклональные антитела и аптамер, блокирующие активность ингибитора пути тканевого фактора, и препарат на основе антисмыслового олигонуклеотида, блокирующий мРНК, ответственную за синтез антитромбина III. Основным преимуществом новых препаратов является то, что они не вызывают выработку антител к факторам свертывания и могут быть использованы для лечения больных с наличием в плазме крови ингибиторов.

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