Triển vọng mới trong điều trị các bệnh tích trữ lysosome

Drugs - Tập 62 - Trang 733-742 - 2012
Raphael Schiffmann1, Roscoe O. Brady1
1Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, USA

Tóm tắt

Mặc dù cá biệt hiếm gặp, các bệnh tích trữ lysosome tạo ra một gánh nặng đáng kể cho xã hội. Đến nay, liệu pháp thay thế enzyme (ERT) đã là phương pháp điều trị thành công nhất cho các bệnh tích trữ lysosome. ERT đảo ngược các biểu hiện hệ thống của bệnh Gaucher nhưng không điều trị hiệu quả các biến chứng thần kinh. Gần đây, ERT đã làm giảm cơn đau thần kinh nặng, ổn định tình trạng bệnh thận và cải thiện chức năng và cấu trúc mạch máu trong các thử nghiệm có kiểm soát giả dược trong thời gian ngắn trên bệnh nhân mắc bệnh Fabry. Cần có các nghiên cứu dài hạn để đánh giá toàn bộ tiềm năng của ERT trong bệnh này. Ở bệnh nhân mắc bệnh Pompe, một rối loạn tim mạch và cơ xương nghiêm trọng, ERT đã cải thiện chức năng và cấu trúc tim, đồng thời tăng cường sức mạnh cơ bắp tổng thể. ERT đã tăng cường sự sống sót ở một số lượng nhỏ trẻ sơ sinh bị ảnh hưởng. ERT cũng đã làm giảm kích thước gan và lách, tăng cường khả năng vận động khớp và chất lượng cuộc sống ở bệnh nhân mắc bệnh mucopolysaccharidosis type I, nhưng khi protein điều trị được tiêm tĩnh mạch, khó có khả năng ảnh hưởng đến kết quả thần kinh trong bệnh này hoặc các rối loạn tương tự khác. Cấy ghép tủy xương tiếp tục hiệu quả trong bệnh Gaucher, trong một số dạng mucopolysaccharidosis và trong các dạng nhẹ của bệnh Krabbé, nhưng nó có tỷ lệ tử vong và biến chứng cao làm hạn chế việc sử dụng trong các bệnh tích trữ lysosome. Các loại thuốc làm chậm tốc độ hình thành các glycolipid tích trữ đang được phát triển và một trong số đó, OGT-918 (N-butyldeoxynojirimycin), đang cho thấy được triển vọng trên bệnh nhân mắc bệnh Gaucher. Liệu pháp gen cho các bệnh tích trữ lysosome có nhiều hứa hẹn như một sự thay thế cho các liệu pháp khác được mô tả ở đây nhưng yêu cầu phát triển nhiều hơn trước khi tiến hành thử nghiệm hiệu quả lâm sàng.

Từ khóa

#bệnh tích trữ lysosome #liệu pháp thay thế enzyme #bệnh Gaucher #bệnh Fabry #bệnh Pompe #cấy ghép tủy xương #liệu pháp gen

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