Hematopoietic Stem Cell Gene Therapy for Wiskott-Aldrich Syndrome.

Wiskott Aldrich Syndrome (WAS) is a fatal primary immunodeficiency disorder caused by mutations in the cytoskeletal adaptor molecule WASP. We here report on our preliminary experience in two patients undergoing hematopoietic stem cell gene therapy upon retroviral WASP gene transfer. Both patients suffered from severe WAS and were treated with 8x10e6 and 7x10e6 /kg body weight transduced CD34 cells, respectively. Follow-up time is 9 and 10 months. Both patients show evidence of gene marking and WAS protein expression in multiple hematopoietic lineages. In particular, WASP-transgenic T and NK cells show a relative increase over time (up to 70% WASP-expressing cells). Both patients show a polyclonal pattern of hematopoiesis, as determined by LAM-PCR. No morphological or cytogenetic abnormalities were observed in the bone marrow. While one patient continues to suffer from autoimmune cytopenia, the other patient has had a marked clinical benefit. This interim analysis documents that hematopoietic gene therapy for WAS is feasible without undue short term toxicity. A longer follow-up period will be required to comprehensively evaluate the clinical and molecular outcome in these patients and to monitor for potential unwanted side-effects.