WAS is a genetic condition caused by errors in a section of DNA on the X chromosome. This reduces a child's ability to fight infection and affects around three in every million children worldwide. WAS affects all the hematopoietic cellular compartments, which explains the broad range of associated clinical manifestations. Severe infection, bleeding, eczema, and autoimmunity are associated with high-risk patients. Patients lacking the functional WAS protein do not survive beyond their second or third decade of life.

Traditionally, WAS patients are treated with allogeneic hematopoietic stem cell transplantation (HSCT) with a human leukocyte antigen-compatible donor. However, this treatment is associated with many hurdles, such as a lack of suitable donors, autoimmune complications, and high mortality rates.

This study presented eight patients with WAS having undergone phase I/II lentiviral vector-based gene therapy in clinical trials where healthy versions of the defective WAS gene were introduced (Nature Medicine, January 24, 2022). Long-term follow up showed this treatment increased the expression of the WAS protein in the patients' cells. Patients experienced clinical resolution of severe eczema and susceptibility to recurrent infections. Both T-cell function and count were restored, memory B cells were switched over time, and patients showed a marked decrease in the frequency and severity of spontaneous bleeding episodes.

Gene therapy for the treatment of WAS is a safe, efficacious treatment for patients who lack a suitable HSCT donor, according to the authors of the study. More efficacious and more reliable transduction protocols and conditioning regimens are likely to improve outcomes further.

"This work shows the potential for gene therapy to act as a safe alternative in WAS patients when transplant is a less favorable option," said Adrian Thrasher, PhD, professor in pediatric immunology at University College London and senior author of the study.