Stem-cell gene therapy for the Wiskott-Aldrich syndrome.
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.).
Department of Pediatric Hematology-Oncology , Hannover Medical School, Hannover, Germany.
Kaan
K
Boztug
Manfred
M
Schmidt
Adrian
A
Schwarzer
Pinaki P
PP
Banerjee
Inés Avedillo
IA
Díez
Ricardo A
RA
Dewey
Marie
M
Böhm
Ali
A
Nowrouzi
Claudia R
CR
Ball
Hanno
H
Glimm
Sonja
S
Naundorf
Klaus
K
Kühlcke
Rainer
R
Blasczyk
Irina
I
Kondratenko
László
L
Maródi
Jordan S
JS
Orange
Christof
C
von Kalle
Christoph
C
Klein
D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000009:adverse effects; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007223:Infant; D008297:Male; D016254:Mutagenesis, Insertional; D014182:Transplantation, Autologous; D014923:Wiskott-Aldrich Syndrome / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000235:genetics*
D051300:Wiskott-Aldrich Syndrome Protein Family