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) on the activity of other sulfatases in fibroblasts from patients with metachromatic leukodystrophy (MLD). We demonstrated that the overexpression of ASA reduces the activity of various sulfatases by a small amount but does not induce an accumulation of glycosaminoglycan. Our results indicate that influence of ASA overexpression on other sulfatases is different from that of N-acetyl-galactosamine-4-sulfatase overexpression reported by Anson et al. We conclude that gene therapy for MLD based on the transfer of a normal ASA gene to mutant cells will be feasible because the overexpression of ASA peptides in cells does not lead to profound deficiency of other sulfatases or result in a new phenotype.
Ohashi
T
T
Department of Pediatrics, Jikei University School of Medicine, Tokyo, Japan.
Matalon
R
R
Barranger
J A
JA
Eto
Y
Y
D002478:Cells, Cultured; D002553:Cerebroside-Sulfatase / Q000096:biosynthesis*; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression; D005822:Genetic Vectors; D006025:Glycosaminoglycans / Q000096:biosynthesis; D006801:Humans; D007966:Leukodystrophy, Metachromatic / Q000201:enzymology / Q000378:metabolism*; D008247:Lysosomes / Q000201:enzymology; D010641:Phenotype; D012190:Retroviridae; D013347:Subcellular Fractions / Q000201:enzymology; D013429:Sulfatases / Q000378:metabolism; D014162:Transfection
D006025:Glycosaminoglycans; D013429:Sulfatases; D002553:Cerebroside-Sulfatase