title: Correction of ADA-SCID by stem cell gene therapy combined with nonmyeloablative conditioning.
abstract: Hematopoietic stem cell (HSC) gene therapy for adenosine deaminase (ADA)-deficient severe combined immunodeficiency (SCID) has shown limited clinical efficacy because of the small proportion of engrafted genetically corrected HSCs. We describe an improved protocol for gene transfer into HSCs associated with nonmyeloablative conditioning. This protocol was used in two patients for whom enzyme replacement therapy was not available, which allowed the effect of gene therapy alone to be evaluated. Sustained engraftment of engineered HSCs with differentiation into multiple lineages resulted in increased lymphocyte counts, improved immune functions (including antigen-specific responses), and lower toxic metabolites. Both patients are currently at home and clinically well, with normal growth and development. These results indicate the safety and efficacy of HSC gene therapy combined with nonmyeloablative conditioning for the treatment of SCID.
authors.affiliation: San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Aiuti
authors.forename: Shimon
authors.initials: S
authors.lastname: Slavin
authors.forename: Memet
authors.initials: M
authors.lastname: Aker
authors.forename: Francesca
authors.initials: F
authors.lastname: Ficara
authors.forename: Sara
authors.initials: S
authors.lastname: Deola
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mortellaro
authors.forename: Shoshana
authors.initials: S
authors.lastname: Morecki
authors.forename: Grazia
authors.initials: G
authors.lastname: Andolfi
authors.forename: Antonella
authors.initials: A
authors.lastname: Tabucchi
authors.forename: Filippo
authors.initials: F
authors.lastname: Carlucci
authors.forename: Enrico
authors.initials: E
authors.lastname: Marinello
authors.forename: Federica
authors.initials: F
authors.lastname: Cattaneo
authors.forename: Sergio
authors.initials: S
authors.lastname: Vai
authors.forename: Paolo
authors.initials: P
authors.lastname: Servida
authors.forename: Roberto
authors.initials: R
authors.lastname: Miniero
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Roncarolo
authors.forename: Claudio
authors.initials: C
authors.lastname: Bordignon
mesh_terms: D000243:Adenosine Deaminase / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology / Q000276:immunology; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D002675:Child, Preschool; D015316:Genetic Therapy; D005822:Genetic Vectors; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D007223:Infant; D007962:Leukocytes / Q000201:enzymology; D019891:Leukopoiesis; D008213:Lymphocyte Activation; D051379:Mice; D016513:Mice, SCID; D012190:Retroviridae / Q000235:genetics; D016511:Severe Combined Immunodeficiency / Q000628:therapy*; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology; D014161:Transduction, Genetic; D019172:Transplantation Conditioning
chemical_list: D007136:Immunoglobulins; D000243:Adenosine Deaminase