Wiskott-Aldrich syndrome (WAS) is an inherited immunodeficiency caused by mutations in the gene encoding WASP that is treated with hematopoietic stem/progenitor cell (HSPC) transplantation. Infusion of autologous HSPCs modified ex vivo by gene therapy is an alternative approach when matched donors are unavailable. Following reduced-intensity conditioning regimen, three WAS patients were infused with autologous HSPCs genetically corrected by lentiviral vector to express functional WASP. All three patients showed stable engraftment of WASP-expressing cells and improvements in platelet counts, immune functions, and clinical score. Lentiviral gene therapy did not induce selection of integrations near oncogenes, and no aberrant clonal expansion was observed. Based on these results, ex vivo lentiviral gene therapy appears a promising treatment for WAS.
Posted by Nicola Brunetti-Pierri, MD