Gene therapy for metachromatic leukodystrophy

Toya Ohashi, Kazuhiko Watabe, Yumi Sato, Izumu Saito, John A. Barranger, Reuben Matalon, Yoshikatsu Eto

Research output: Contribution to journalArticle

5 Scopus citations


Metachromatic leukodystrophy (MLD) is an inherited metabolic disease which is characterized by a deficiency of arylsulfatase A (ASA). This deficiency causes progressive accumulation of cerebroside sulfate in oligodendrocytes (OL) in the brain, resulting in dysmyelination. Approaches being developed by the authors to treating MLD are based on direct delivery of ASA genes into the brain. In the present report, it has been shown that the recombinant adenovirus (Adex ISRLacZ) was able to transduce the OL very efficiently. Moreover, primary fibroblasts from MLD patients were exposed to recombinant adenovirus expressing the ASA gene (Adex ISRASA) and the cells expressed the transgene. The influence of overexpression of ASA on the activity of other sulfatases was also tested in fibroblasts from patients with MLD using a retrovirus vector (MFG-ASA). It was demonstrated that the overexpression of ASA reduces the activity of various sulfatases by a small amount but does not induce an accumulation of glycosaminoglycan. These results indicate that the influence of ASA overexpression on other sulfatases is different from that of the N-acetygalactosamine-4-sulfatase overexpression in a previous report. It was concluded that the correction of ASA deficiency by a recombinant adenovirus that potentially could be used to transfer the gene to the brain, and gene therapy for MLD based on gene transfer of the ASA gene to mutant cells will be feasible because the overexpression of ASA in cells does not lead to profound deficiency of other sulfatases or result in a new phenotype.

Original languageEnglish (US)
Pages (from-to)193-201
Number of pages9
JournalActa Paediatrica Japonica (Overseas Edition)
Issue number2
StatePublished - Apr 1996
Externally publishedYes



  • adenovirus
  • gene therapy
  • metachromatic leukodystrophy
  • retrovirus
  • sulfatase

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Ohashi, T., Watabe, K., Sato, Y., Saito, I., Barranger, J. A., Matalon, R., & Eto, Y. (1996). Gene therapy for metachromatic leukodystrophy. Acta Paediatrica Japonica (Overseas Edition), 38(2), 193-201.