Hematopoietic stem cell gene therapy provides hope for Wiskott-Aldrich syndrome patientsPublished: April 12, 2019
Scientists at San Raffaele Telethon Institute for Gene Therapy have published follow-up results of a Phase 1/2 gene therapy trial conducted in Wiskott-Aldrich syndrome patients. Interim analysis conducted 3 years after the first six pediatric patients were treated with the lentiviral vector-derived gene therapy reveals the therapy to be safe and effective for treating Wiskott-Aldrich syndrome.
Wiskott-Aldrich syndrome is a rare, life-threatening, X-linked primary immunodeficiency caused by mutations in the WAS gene which encodes the WAS protein (WASP), a cytoskeletal regulator which is expressed exclusively in hematopoietic cells.
Transplanting allogeneic hematopoietic stem/progenitor cells (HSPCs) is effective when matched donors are available. For patients without matched donors, an alternative therapeutic strategy is the use of autologous HSPCs that have been genetically corrected ex vivo.
The present trial sponsored by London-based Orchard Therapeutics and Milan-based San Raffaele Telethon Institute for Gene Therapy used self-inactivating lentiviral vectors encoding functional WASP to genetically correct HSPCs. The corrected cells were reinfused into the patient after a reduced-intensity conditioning regimen. Interim analysis was conducted 3 years after the first six patients were treated with the HSPC gene therapy.
Safety of the conditioning regimen and that of the lentiviral gene transfer were the primary safety endpoints. The primary efficacy endpoints were overall survival, sustained engraftment of genetically corrected HSPCs, expression of vector-derived WASP, improved T cell function and improved platelet count.
All the patients who received the treatment was well after 3 years. Data showed stable engraftment of WASP-expressing cells and improvements in platelet counts, immune functions and clinical scores. Even though patient platelets remained lower than that of normal, they could still lead a normal life. The patients showed improved immune function and amelioration of clinical manifestations of the disease, including protection from bleeding and severe infections as well as resolution of eczema.
Findings from the study published in the Lancet Hematology demonstrate HSPC gene therapy as a valuable treatment option for patients with severe Wiskott-Aldrich syndrome, particularly for those who do not have a suitable HSPC donor available.
The team has now started another clinical trial where they are testing the safety and efficacy frozen stem cells in Wiskott-Aldrich syndrome patients. Freezing the cells after they are genetically modified with the lentiviral vectors would be a way to make the therapy more widely available.
Source: Lentiviral haemopoietic stem/progenitor cell gene therapy for treatment of Wiskott-Aldrich syndrome: interim results of a non-randomised, open-label, phase 1/2 clinical study. Ferrua F et al., The Lancet Hematology, April 2019. DOI