Abstract
Fabry disease is an X-linked inherited metabolic disorder caused by a deficiency of α-galactosidase (α-gal), resulting in the accumulation of ceramide trihexoside (CTH) in body fluids and in many organs and tissues. We constructed a recombinant adenovirus with a human α-gal cDNA (AxCAG α-gal), and transfected this vector to skin fibroblasts from Fabry patients. Transfected cells expressed high amounts of α-gal in their cytoplasm, and a high level of α-gal activity was detected in the medium. The accumulated CTH in the fibroblasts disappeared 3 days after infection. The secreted α-gal also eliminated the accumulated CTH from uninfected patient's cells. The enzyme may be taken up through mannose-6-phosphate receptors, as the addition of mannose-6-phosphate to the medium completely inhibited the uptake of the enzyme. The infected cells continued to express α-gal for more than 10 days. These results suggest that AxCAG α-gal could be used as enzyme replacement gene therapy for Fabry disease.
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Received: July 27, 1999 / Accepted: September 16, 1999
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Ohsugi, K., Kobayashi, K., Itoh, K. et al. Enzymatic corrections for cells derived from Fabry disease patients by a recombinant adenovirus vector. J Hum Genet 45, 1–5 (2000). https://doi.org/10.1007/s100380050001
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DOI: https://doi.org/10.1007/s100380050001