Retrovirally expressed human arylsulfatase A corrects the metabolic defect of arylsulfatase A-deficient mouse cells.

A deficiency of arylsulfatase A (ASA) causes the lysosomal storage disease metachromatic leukodystrophy (MLD) which is characterized primarily by demyelination of the central nervous system. ASA-deficient mice develop a disease which resembles MLD in many respects and thus serve as an appropriate animal model for this disease. To establish gene therapy protocols for ASA-deficient mice, we constructed two retroviral vectors based on the murine stem cell virus. Both vectors harbor the human ASA cDNA controlled by the retroviral promoter/enhancer element, but differ by the presence or absence of a neomycin resistance gene driven by an internal promoter. A comparative analysis of the one- versus the two-gene vector and an amphotropic versus an ecotropic producer cell line revealed that the amphotropic producer cell line for the one-gene vector transfers ASA overexpression to the target cells most efficiently. The human ASA encoded by this vector is correctly expressed in heterologous mouse cells and corrects the metabolic defect of transduced ASA-deficient murine cells. The constructed one-gene vector might thus be a potentially useful tool for the development of a gene-based therapy for ASA-deficient mice. Gene Therapy (2000) 7, 805-812.