GENE THERAPY FOR WISKOTT-ALDRICH SYNDROME IN A SEVERELY AFFECTED ADULT

Until recently hematopoietic stem cell transplantation was the only curative option for Wiskott-Aldrichsyndrome (WAS). The first attempts at gene therapy for WAS using a B-retroviral vector improvedimmunological parameters substantially but were complicated by acute leukemia as a result of insertionalmutagenesis in a high proportion of patients. More recently treatment of children with a state-of-the-artself-inactivating lentiviral vector (LV-w1.6 WASp) has resulted in significant clinical benefit withoutinducing selection of clones harbouring integrations near oncogenes. Here, we describe a case of a presplenectomised30 year old patient with severe WAS manifesting as cutaneous vasculitis, inflammatoryarthropathy, intermittent polyclonal lymphoproliferation, significant chronic kidney disease and requiringlong-term immunosuppressive treatment. Following reduced intensity conditioning there was rapidengraftment and expansion of a polyclonal pool of transgene-positive functional T cells, and sustainedgene marking in myeloid and B cell lineages up to 20 months of observation. The patient was able todiscontinue immunosuppression and exogenous immunoglobulin support, with improvement in vasculiticdisease and pro-inflammatory markers. Autologous gene therapy using a lentiviral vector is a viablestrategy for adult WAS patients with severe chronic disease complications and for whom an allogeneicprocedure could present an unacceptable risk. This trial was registered at ClinicalTrials.gov #NCT01347242.