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Molecular and Cellular Biology of Platelet Formation pp 383–398Cite as

Cellular Therapies for Wiskott-Aldrich Syndrome

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Abstract

Wiskott-Aldrich syndrome (WAS) is an X-linked inherited rare disease caused by mutations of the WAS gene and affecting various subsets of the hematopoietic system. Affected patients experience severe bleedings, autoimmunity, immunodeficiency, and an increased risk of hematopoietic malignancies. Since several decades, patients with WAS have been treated successfully using allogeneic hematopoietic stem cell transplantation – this procedure may however be associated with significant morbidity as well as mortality, in particular in case of HLA-disparity. Hematopoietic stem cell gene therapy has been developed as an alternative, but oncogene activation secondary to insertional mutagenesis can lead to oncogenesis. More recent therapeutic approaches include the use of self-inactivating lentiviral vectors, promising a better safety-to-risk ratio. Therapeutic efficacy and safety are currently being assessed. New methods of genomic engineering employing zinc finger nucleases, TALENs, and CRISPR-Cas as tools may offer new perspectives to site-specific genomic repair of disease-causing mutations.

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Authors and Affiliations

  1. Dr. von Hauner Children’s Hospital, Ludwig-Maximilians-Universtität München, Lindwurmstraße 4, Munich, 80337, Germany

    Christian J. Braun & Christoph Klein

  2. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA

    Christian J. Braun

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  1. Institute of Experimental Biomedicine I, University Hospital Würzburg, Würzburg, Germany

    Harald Schulze

  2. Vascular Biology Programm, Harvard Medical School, Boston, Massachusetts, USA

    Joseph Italiano

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Braun, C.J., Klein, C. (2016). Cellular Therapies for Wiskott-Aldrich Syndrome. In: Schulze, H., Italiano, J. (eds) Molecular and Cellular Biology of Platelet Formation. Springer, Cham. https://doi.org/10.1007/978-3-319-39562-3_18

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