GENETIC THERAPY OF FABRY DISEASE

法布里病的基因治疗

• 批准号: 2579673
• 负责人: R O BRADY
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2579673
• 关键词: Fabry's disease; Retroviridae; alpha galactosidase; clinical research; clinical trial phase I; complementary DNA; enzyme activity; gene therapy; genetic transduction; hematopoietic stem cells; human genetic material tag; human subject; human therapy evaluation; inborn lysosomal enzyme disorder; inborn metabolism disorder; sex linked trait; transfection /expression vector

Fabry disease is an X-linked inherited recessive metabolic disorder caused by insufficient activity of the lysosomal enzyme alpha- galactosidase A (ceramidetrihexosidase). In contrast with the remarkable benefit of enzyme replacement therapy developed by DMNB for patients with Gaucher disease, little progress has been made concerning specific treatment for patients with Fabry disease. We propose to develop gene replacement therapy for patients with this metabolic disorder. Retroviral vectors containing the cDNA of human alpha-galactosidase A will be produced, and the efficiency of transduction of patients' hematopoietic stem cells will be determined. When a vector with sufficient activity and titer is available, we shall develop a Phase l gene therapy trial for patients with Fabry disease.

法布里病是一种X连锁隐性遗传性代谢紊乱 由于溶酶体酶α- 半乳糖苷酶A（神经酰胺三己糖苷酶）。与非凡的相比， DMNB开发的酶替代疗法对 戈谢病，关于具体的进展甚微， 治疗法布里病患者。 我们建议为这种患者开发基因替代疗法。 代谢紊乱 含有人cDNA的逆转录病毒载体 将产生α-半乳糖苷酶A，并且 将确定患者造血干细胞的转导。 当有足够活性和效价的载体时，我们将 为法布里病患者开展I期基因治疗试验。