Stem-cell gene therapy for the Wiskott-Aldrich syndrome
| Autor: | Christoph Klein, László Maródi, Adrian Schwarzer, Ali Nowrouzi, Claudia R. Ball, Klaus Kühlcke, Ricardo A Dewey, Manfred Schmidt, Irina Kondratenko, Sonja Naundorf, Marie Böhm, Rainer Blasczyk, Christof von Kalle, Kaan Boztug, Jordan S. Orange, Inés Avedillo Díez, Hanno Glimm, Pinaki P. Banerjee |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Wiskott–Aldrich syndrome Genetic enhancement medicine.medical_treatment Hematopoietic stem cell transplantation medicine.disease_cause Klinikai orvostudományok Transplantation Autologous Article Autoimmunity Cell therapy 03 medical and health sciences 0302 clinical medicine medicine Humans 030304 developmental biology 0303 health sciences business.industry Gene Transfer Techniques Hematopoietic Stem Cell Transplantation Infant General Medicine Orvostudományok Genetic Therapy medicine.disease 3. Good health Wiskott-Aldrich Syndrome Wiskott-Aldrich Syndrome Protein Family Haematopoiesis Mutagenesis Insertional 030220 oncology & carcinogenesis Immunology Primary immunodeficiency Stem cell business |
| Zdroj: | The New England journal of medicine. 363(20) |
| ISSN: | 1533-4406 |
| Popis: | 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.). |
| Databáze: | OpenAIRE |
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