[HTML][HTML] Stem-cell gene therapy for the Wiskott–Aldrich syndrome

K Boztug, M Schmidt, A Schwarzer… - … England Journal of …, 2010 - Mass Medical Soc
K Boztug, M Schmidt, A Schwarzer, PP Banerjee, IA Díez, RA Dewey, M Böhm, A Nowrouzi
New England Journal of Medicine, 2010Mass Medical Soc
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' …
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.)
The New England Journal Of Medicine