Ohashi T, Matalon R, Barranger J A, Eto Y
Department of Pediatrics, Jikei University School of Medicine, Tokyo, Japan.
Gene Ther. 1995 Aug;2(6):363-8.
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.
我们测试了芳基硫酸酯酶A（ASA）过表达对异染性脑白质营养不良（MLD）患者成纤维细胞中其他硫酸酯酶活性的影响。我们证明，ASA的过表达会使各种硫酸酯酶的活性略有降低，但不会诱导糖胺聚糖的积累。我们的结果表明，ASA过表达对其他硫酸酯酶的影响与Anson等人报道的N-乙酰半乳糖胺-4-硫酸酯酶过表达的影响不同。我们得出结论，基于将正常ASA基因转移到突变细胞的MLD基因治疗将是可行的，因为细胞中ASA肽的过表达不会导致其他硫酸酯酶的严重缺乏或产生新的表型。
