title: Gene therapy for the Wiskott-Aldrich syndrome.
abstract: BACKGROUND
  Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency (PID) characterized by micro-thrombocytopenia, recurrent infections, eczema, which is associated with a high incidence of auto-immunity and lymphoreticular malignancy. One of the first diseases to be successfully treated by allogeneic hematopoietic stem cell transplantation, WAS is currently the subject of several phase I/II gene therapy trials for patients without HLA-compatible donors.
  
  
  OBJECTIVE
  This article reviews the preclinical and clinical data leading to the development of gene therapy of WAS with lentiviral vectors.
  
  
  RESULTS
  A recent clinical trial using a conventional gammaretroviral vector has demonstrated the proof of principle of gene therapy in WAS, but has also highlighted a common limitation of the technology. Encouraging preclinical efficacy and safety results using refined lentiviral vectors, and the development of robust clinical-grade manufacturing processes have supported the initiation of several phase I/II new studies.
  
  
  CONCLUSIONS
  WAS is amenable to hematopoietic stem cell gene therapy. New trials using lentiviral vectors are expected to improve efficacy and safety profiles. Beyond proof of principle, ongoing international efforts to coordinate trials of gene therapy for the WAS may also provide a model for the expedited development of new treatments for other rare diseases.
authors.affiliation: Inserm, U951, Molecular Immunology and Innovative Biotherapies, Genethon, Evry, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Galy
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Thrasher
mesh_terms: D002986:Clinical Trials as Topic; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics*; D018380:Hematopoietic Stem Cell Transplantation; D057166:High-Throughput Screening Assays; D006801:Humans; D016086:Lentivirus / Q000235:genetics*; D013921:Thrombocytopenia; D014923:Wiskott-Aldrich Syndrome / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy*; D051316:Wiskott-Aldrich Syndrome Protein / Q000235:genetics
chemical_list: D051316:Wiskott-Aldrich Syndrome Protein