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.
