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Gene therapy for Wiskott-Aldrich syndrome in a severely affected adult

Morris, EC; Fox, T; Chakraverty, R; Tendeiro, R; Snell, K; Rivat, C; Grace, S; ... Thrasher, AJ; + view all (2017) Gene therapy for Wiskott-Aldrich syndrome in a severely affected adult. Blood , 130 pp. 1327-1335. 10.1182/blood-2017-04-777136. Green open access

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Abstract

Until recently hematopoietic stem cell transplantation was the only curative option for Wiskott-Aldrich syndrome (WAS). The first attempts at gene therapy for WAS using a ϒ-retroviral vector improved immunological parameters substantially but were complicated by acute leukemia as a result of insertional mutagenesis in a high proportion of patients. More recently treatment of children with a state-of-the-art self-inactivating lentiviral vector (LV-w1.6 WASp) has resulted in significant clinical benefit without inducing selection of clones harbouring integrations near oncogenes. Here, we describe a case of a pre-splenectomised 30 year old patient with severe WAS manifesting as cutaneous vasculitis, inflammatory arthropathy, intermittent polyclonal lymphoproliferation, significant chronic kidney disease and requiring long-term immunosuppressive treatment. Following reduced intensity conditioning there was rapid engraftment and expansion of a polyclonal pool of transgene-positive functional T cells, and sustained gene marking in myeloid and B cell lineages up to 20 months of observation. The patient was able to discontinue immunosuppression and exogenous immunoglobulin support, with improvement in vasculitic disease and pro-inflammatory markers. Autologous gene therapy using a lentiviral vector is a viable strategy for adult WAS patients with severe chronic disease complications and for whom an allogeneic procedure could present an unacceptable risk. This trial was registered at ClinicalTrials.gov #NCT01347242.

Type: Article
Title: Gene therapy for Wiskott-Aldrich syndrome in a severely affected adult
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1182/blood-2017-04-777136
Publisher version: https://doi.org/10.1182/blood-2017-04-777136
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Renal Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/1566966
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