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Science. 2013 Aug 23;341(6148):1233151. doi: 10.1126/science.1233151. Epub 2013 Jul 11.

Lentiviral hematopoietic stem cell gene therapy in patients with Wiskott-Aldrich syndrome.

Author information

1
San Raffaele Telethon Institute for Gene Therapy, Division of Regenerative Medicine, Stem Cells, and Gene Therapy, San Raffaele Scientific Institute, 20132 Milan, Italy. aiuti.alessandro@hsr.it

Abstract

Wiskott-Aldrich syndrome (WAS) is an inherited immunodeficiency caused by mutations in the gene encoding WASP, a protein regulating the cytoskeleton. Hematopoietic stem/progenitor cell (HSPC) transplants can be curative, but, when matched donors are unavailable, infusion of autologous HSPCs modified ex vivo by gene therapy is an alternative approach. We used a lentiviral vector encoding functional WASP to genetically correct HSPCs from three WAS patients and reinfused the cells after a reduced-intensity conditioning regimen. All three patients showed stable engraftment of WASP-expressing cells and improvements in platelet counts, immune functions, and clinical scores. Vector integration analyses revealed highly polyclonal and multilineage haematopoiesis resulting from the gene-corrected HSPCs. Lentiviral gene therapy did not induce selection of integrations near oncogenes, and no aberrant clonal expansion was observed after 20 to 32 months. Although extended clinical observation is required to establish long-term safety, lentiviral gene therapy represents a promising treatment for WAS.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01515462.

PMID:
23845947
PMCID:
PMC4375961
DOI:
10.1126/science.1233151
[Indexed for MEDLINE]
Free PMC Article

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