Hematopoietic stem cell gene therapy for Wiskott Aldrich syndrome.

K BOZTUG; C KLEIN; INES AVEDILLO DÍEZ; R. A. DEWEY; A SCHWARZER; J DIESTELHORST; S NAUNDORF; K KUHLCKE; K SCHWARZWAELDER; M SCHMIDT; C VON KALLE; P BANJEREE; J ORANGE; I KONDRATENKO; L MARODI; K WELTE

's-Hertogenbosch, The Netherlands.

Congreso; XIIIth European Society for Immunodeficiencies (ESID) Meeting,; 2008

Wiskott Aldrich Syndrome is a life-threatening immunodeficiency disorder characterized by bleeding secondary to microthrombocytopenia, recurrent infections, autoimmunity, and susceptibility to lymphoma. We here present a preliminary analysis of the first two patients treated by infusion of autologous hematopoietic stem cells transduced with a retroviral vector expressing WASP. Both patients showed evidence of long-term gene marking in myeloid and lymphoid cells. Importantly, the majority of peripheral thrombocytes showed evidence of WASP expression. Functional reconstitution was documented in dendritic cells (podosome formation), T-cells (proliferation in response to CD3-signaling), and NK-cells (formation of immunological synapse). Clinically, patients are in excellent condition more than 18 months after gene therapy. Of note, they did not develop any severe infections or bleeding. Eczema and  autoimmunity resolved completely. Molecular insertion site analysis yielded a polyclonal pattern of hematopoiesis. In sum, hematopoietic stem cell gene therapy may be of benefit for patients with WASP deficiency more extensive studies and longer follow-up are needed to determine the safety profile of this experimental therapeutic approach.