Metabolic correction of congenital erythropoietic porphyria by
retrovirus-mediated gene transfer into Epstein-Barr virus-transformed B-
cell lines
F Moreau-Gaudry, F Mazurier, M Bensidhoum, C Ged and H de Verneuil
Laboratoire de Biochimie Medicale et Biologie Moleculaire, Universite de
Bordeaux II, France.
Congenital erythropoietic porphyria (CEP) is an inherited metabolic
disorder resulting from the accumulation of porphyrins because of defective
uroporphyrinogen III synthase (UROIIIS). This autosomal recessive disorder
is phenotypically heterogeneous with respect to the age of onset and the
severity of the symptoms. Different exonic point mutations in the UROIIIS
gene have been identified, providing phenotype- genotype correlations in
this disease. Severe cases may be treated by bone marrow transplantation
and are potential candidates for somatic gene therapy. Epstein-Barr
virus-transformed B-cell lines from patients with CEP provide a model
system for the disease. We have used retrovirus-mediated expression of
UROIIIS to restore enzymatic activity in a B-cell line from a patient. We
have also demonstrated the metabolic correction of the disease, ie,
porphyrin accumulation into the deficient transduced cells was reduced to
the normal level. These data show the potential of gene therapy for this
disease.
Volume 85,
Issue 6,
pp. 1449-1453,
03/15/1995
Copyright © 1995 by The American Society of Hematology
