title: [Successful gene therapy of mice with congenital erythropoietic porphyria].
abstract: Porphyrias are a group of disorders due to a genetic deficiency in one of the heme biosynthetic pathway enzymes. Congenital erythropoietic porphyria (CEP) is the most severe type characterized by a deficiency in uroporphyrinogen III synthase (UROS) activity. Bone marrow transplantation represents a curative treatment for patients, as long as human leucocyte antigen-compatible donor is available. We used a recently obtained murine model to check the feasibility of gene therapy in this disease. Lentivirus-mediated transfer of the human UROS cDNA into hematopoietic stem cells (HSCs) from Uros(mut 248) mice resulted in a complete and long-term enzymatic, metabolic and phenotypic correction of the disease, favored by a survival advantage of corrected red blood cells. These results demonstrate for the first time that the cure of this mouse model of CEP at moderate transduction level supports the proof of concept of a gene therapy in this disease by transplantation of genetically modified HSCs.
authors.affiliation: Inserm, U876, Université Victor Segalen-Bordeaux 2, Bordeaux, France. verneuil@u-bordeaux2.fr
authors.forename: Hubert
authors.initials: H
authors.lastname: de Verneuil
authors.forename: Elodie
authors.initials: E
authors.lastname: Robert-Richard
authors.forename: Cécile
authors.initials: C
authors.lastname: Ged
authors.forename: Frédéric
authors.initials: F
authors.lastname: Mazurier
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Richard
authors.forename: François
authors.initials: F
authors.lastname: Moreau-Gaudry
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D051379:Mice; D017092:Porphyria, Erythropoietic / Q000235:genetics* / Q000628:therapy*