Correction of ADA-SCID by stem cell gene therapy combined with nonmyeloablative conditioning

Science. 2002 Jun 28;296(5577):2410-3. doi: 10.1126/science.1070104.

Alessandro Aiuti ¹, Shimon Slavin, Memet Aker, Francesca Ficara, Sara Deola, Alessandra Mortellaro, Shoshana Morecki, Grazia Andolfi, Antonella Tabucchi, Filippo Carlucci, Enrico Marinello, Federica Cattaneo, Sergio Vai, Paolo Servida, Roberto Miniero, Maria Grazia Roncarolo, Claudio Bordignon

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Affiliation

1 San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Milan, Italy.

PMID: 12089448 DOI: 10.1126/science.1070104

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.

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