Retrovirally expressed human arylsulfatase A corrects the metabolic defectof arylsulfatase A-deficient mouse cells

A deficiency of arylsulfatase A (ASA) causes the lysosomal storage disease metachromatic leukodystrophy (MLD) which is characterized primarily by demy elination of the central nervous system. ASA-deficient mice develop a disea se which resembles MLD in many respects and thus serve as an appropriate an imal model for this disease. To establish gene therapy protocols for ASA-de ficient mice, we constructed two retroviral vectors based on the murine ste m cell virus. Both vectors harbor the human ASA cDNA controlled by the retr oviral promoter/enhancer element, but differ by the presence or absence of a neomycin resistance gene driven by an internal promoter. A comparative an alysis of the one-versus the two-gene vector and an amphotropic versus an e cotropic producer cell line revealed that the amphotropic producer cell lin e for the one-gene vector transfers ASA overexpression to the target cells most efficiently. The human ASA encoded by this vector is correctly express ed in heterologous mouse cells and corrects the metabolic defect of transdu ced ASA-deficient murine cells. The constructed one-gene vector might thus be a potentially useful tool for the development of a gene-based therapy fo r ASA-deficient mice.