Stem-Cell Gene Therapy for the Wiskott-Aldrich Syndrome.

K. BOZTUG; M. SCHMIDT; A. SCHWARZER; P. P. BANERJEE; I. AVEDILLO DÍEZ; R. A. DEWEY; M. BÖHM; C. BALL; A. NOWROUZI; S. NAUNDORF; K. KUHLCKE; R. BLASCZYKS; I. KONDRATENKO; L. MARODI; J.S. ORANGE; C. VON KALLE; C. KLEIN

NEW ENGLAND JOURNAL OF MEDICINE

Massachusetts Medical Society

Lugar: Waltham, MA; Año: 2010 vol. 363 p. 1918 - 1927

0028-4793

Wiskott-Aldrich syndrome (WAS) is a primary immunodeficiency disorder associated with thrombocytopenia, eczema and autoimmunity. We treated two WAS patients by transfusion of autologous, genetically modified hematopoietic stem cells (HSC). We demonstrate sustained WAS protein (WASP) expression in HSC, lymphoid and myeloid cells, and platelets after gene therapy. T and B lymphocytes, natural killer (NK) cells, and monocytes were functionally corrected. The patients´ clinical condition markedly improved with respect to hemorrhagic diathesis, eczema, autoimmunity, and predisposition to severe infections. Comprehensive insertion site analysis demonstrated vector integration that targeted multiple genes controlling growth development and immunological responses in a persistently polyclonal hematopoiesis.