Abstract
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 (Adex1SRLacZ) was able to transduce the OL very efficiently. Moreover, primary fibroblasts from MLD patients were exposed to recombinant adenovirus expressing the ASA gene (Adex1SRASA) 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.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.