Genes & CellsGenes & CellsГены и КлеткиGenes and Cells2313-18292500-2562Human Stem Cells Institute12202710.23868/202003002ArticlesСтатьиReview ArticleTay-Sachs disease: diagnostic, modeling and treatment approachesБолезнь Тея-Сакса: диагностика, моделирование и подходы к терапииSolovyevaV. VСоловьеваВ. ВShaimardanovaA. AШаймардановаА. АChulpanovaD. SЧулпановаД. СKitaevaK. VКитаеваК. ВRizvanovA. AРизвановА. Аrizvanov@gmail.comKazan (Volga region) Federal UniversityКазанский (Приволжский) федеральный университет15032020151VOL 15, NO1 (2020)ТОМ 15, №1 (2020)172216012023Copyright ©; 2020, Eco-VectorCopyright ©; 2020, Эко-Вектор2020Eco-VectorЭко-Векторhttps://genescells.ru/2313-1829/article/view/122027

Tay-Sachs disease (OMIM 272800) belongs to the group of autosomal-recessive disorders, caused by p-hexosaminidase A (HexA) enzyme deficiency, resulting in GM2-ganglioside accumulation in nervous and other tissues of the body. Enzyme deficiency is caused by various mutations in HEXA gene. Clinical symptom severity depends on residual HexA enzymatic activity associated with some mutations. Currently, there is no effective treatment for Tay-Sachs disease. There are clinical reports of substrate reduction therapy, bone marrow or umbilical cord blood transplantation. However, the therapeutic efficacy of these methods remains insufficient to prevent aggravation of neurological symptoms in Tay-Sachs disease patients. Encouraging results were obtained using gene therapy to deliver wild-type genes encoding the а and p subunits of HexA. This review discusses the therapeutic strategies in Tay-Sachs disease treatment, as well as diagnostic methods and existing animal models to evaluate the effectiveness of new approaches for Tay-Sachs disease therapy.

Болезнь Тея-Сакса (OMIM 272800) - наследственное аутосомно-рецессивное заболевание, обусловленное дефицитом фермента р-гексозаминидазы А (HexA), в результате чего происходит накопление GM2-ганглиозидов в нервной и других тканях организма. Дефицит фермента возникает вследствие различных мутаций гена HEXA. Тяжесть клинических признаков при болезни Тея-Сакса определяется остаточной активностью HexA, зависящей от типа (вида) мутации. В настоящее время не существует эффективного лечения болезни Тея-Сакса. Описаны клинические случаи применения субстрат-редуцирующей терапии, трансплантации костного мозга или пуповинной крови, однако терапевтическая эффективность данных методов остается недостаточной для предотвращения усугубления неврологических нарушений у пациентов с болезнью Тея-Сакса. Обнадеживающие результаты получены с использованием методов генной терапии для доставки генов дикого типа, кодирующих а и р субъединицы фермента HexA. В настоящем обзоре обсуждаются терапевтические стратегии лечения болезни Тея-Сакса, а также методы диагностики и моделирование этой патологии на животных для оценки эффективности новых методов терапии болезни Тея-Сакса.

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