OVEREXPRESSION OF ARYLSULFATASE-A GENE IN FIBROBLASTS FROM METACHROMATIC LEUKODYSTROPHY PATIENTS DOES NOT INDUCE A NEW PHENOTYPE

We tested the influence of overexpression of arylsulfatase A (ASA) act ivity of other sulfatases in fibroblasts from patients with metachroma tic leukodystrophy (MLD). We demonstrated that the overexpression of A SA reduces the activity of various sulfatases by a small amount but do es not induce an accumulation of glycosaminoglycan. Our results indica te that influence of ASA overexpression on other sulfatases is differe nt from that of N-acetyl-galactosamine-4-sulfatase overexpression repo rted by Anson et al.(1) We conclude that gene therapy for MLD based on the transfer of a normal ASA gene to mutant cells will be feasible be cause the overexpression of ASA peptides in cells does not lead to pro found deficiency of other sulfatases or result in a new phenotye.