[Molecular diagnosis and gene therapy for Gaucher disease].

Gaucher disease is the most prevalent lysosomal storage disease. It is caused by deficient activity of a lysosomal enzyme known as glucocerebrosidase, also called glucosylceramidase, resulting from mutations in the gene encoding the enzyme. The numerous mutations in glucocerebrosidase gene from patients were reported and the correlation of phenotype and genotype were studied. However, a given genotype cannot be uniquely correlated with a specific phenotype. In the therapeutic point of view, two successful treatment were developed based on the correction of the enzyme deficiency in macrophages. These are bone marrow transplantation and enzyme infusion therapy. Although patients have responded to these two therapies, inherent problems limit their application. Thus, these problems makes Gaucher disease an excellent candidate for therapy based on gene transfer to hematopoietic cells. We succeeded in efficient transduction and sustained high expression of glucocerebrosidase gene in mouse hematopoietic stem cells and macrophages from long term reconstituted mice. The results of our study strengthen the rationale for gene therapy as a treatment for Gaucher disease.