Stem-cell gene therapy for the Wiskott-Aldrich syndrome

Kaan Boztug, Manfred Schmidt, Adrian Schwarzer, Pinaki P. Banerjee, Inés Avedillo Díez, Ricardo A. Dewey, Marie Böhm, Ali Nowrouzi, Claudia R. Ball, Hanno Glimm, Sonja Naundorf, Klaus Kühlcke, Rainer Blasczyk, Irina Kondratenko, László Maródi, Jordan S. Orange, Christof Von Kalle, Christoph Klein

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Abstract

The Wiskott-Aldrich syndrome (WAS) is an X-linked recessive primary immunodeficiency disorder associated with thrombocytopenia, eczema, and autoimmunity. We treated two patients who had this disorder with a transfusion of autologous, genetically modified hematopoietic stem cells (HSC). We found sustained expression of WAS protein expression in HSC, lymphoid and myeloid cells, and platelets after gene therapy. T and B cells, natural killer (NK) cells, and monocytes were functionally corrected. After treatment, the patients' clinical condition markedly improved, with resolution of hemorrhagic diathesis, eczema, autoimmunity, and predisposition to severe infection. Comprehensive insertion-site analysis showed vector integration that targeted multiple genes controlling growth and immunologic responses in a persistently polyclonal hematopoiesis. (Funded by Deutsche Forschungsgemeinschaft and others; German Clinical Trials Register number, DRKS00000330.).

Original languageEnglish
Pages (from-to)1918-1927
Number of pages10
JournalNew England Journal of Medicine
Volume363
Issue number20
DOIs
Publication statusPublished - Nov 11 2010

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ASJC Scopus subject areas

  • Medicine(all)

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Boztug, K., Schmidt, M., Schwarzer, A., Banerjee, P. P., Díez, I. A., Dewey, R. A., Böhm, M., Nowrouzi, A., Ball, C. R., Glimm, H., Naundorf, S., Kühlcke, K., Blasczyk, R., Kondratenko, I., Maródi, L., Orange, J. S., Von Kalle, C., & Klein, C. (2010). Stem-cell gene therapy for the Wiskott-Aldrich syndrome. New England Journal of Medicine, 363(20), 1918-1927. https://doi.org/10.1056/NEJMoa1003548