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Stem-Cell Gene Therapy for the Wiskott–Aldrich Syndrome

2010; Massachusetts Medical Society; Volume: 363; Issue: 20 Linguagem: Inglês

10.1056/nejmoa1003548

1533-4406

Kaan Boztuğ, 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,

Viral Infectious Diseases and Gene Expression in Insects

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.).