Gene therapy effectively treats complications of Wiskott-Aldrich syndrome in children

In a small cohort of children and adolescents with Wiskott-Aldrich syndrome, autologous hematopoietic stem cell gene therapy led to clinical improvements in symptoms of autoimmunity, infectious complications and severe eczema, according to a press release.

Wiskott-Aldrich syndrome is a rare immunodeficiency disorder that is caused by loss-of-function mutations in the WAS gene. Characterized by eczema, recurring infections and thrombocytopenia, most patients with Wiskott-Aldrich syndrome do not survive beyond their 20s or 30s, according to background information provided in the study.             

Salima Hacein-Bey Abina, PharmD, PHD, of the biotherapy department at Necker Children’s Hospital in Paris, France, and colleagues assessed the outcomes and safety of gene-corrected autologous hematopoietic stem cell gene therapy infused into seven patients with severe Wiskott-Aldrich syndrome who lacked HLA antigen-matched related or unrelated stem cell donors. Patients previously underwent myeloablative therapy.

The mean age of patients was 7 years. All patients were treated between December 2010 and January 2014 in France and England. The intermediate findings include follow-up data between 9 and 42 months.

Clinical improvements were observed among six of the seven patients after undergoing gene therapy and treatment was well-tolerated. However, at 7 months after treatment, complications from a preexisting treatment-refractory herpes virus infection led to death in one patient.

Signs and symptoms of autoimmunity improved in 5 patients; eczema resolved in all six of the surviving patients. After gene therapy, infectious complications were resolved in all six patients; prophylactic antibiotic therapy was discontinued in three cases.

Moreover, days of hospitalization were reduced from a median of 25 days for the 2 years before treatment to 0 days during the 2 years after treatment. There were no severe bleeding episodes that occurred after treatment and all patients were free of blood product support, according to the press release.

In an accompanying editorial, Harry L. Malech, MD, of the NIH, and Hans D. Ochs, MD, of the University of Washington and Seattle Children’s Research Institute, wrote: “This study provides strong evidence that this type of gene therapy achieves substantial restoration of immune function associated with prolonged clinical benefit to patients with severe Wiskott-Aldrich syndrome.”

Disclosure: Abina reports no relevant financial disclosures. Please see the full study for a list of all other authors’ relevant financial disclosures.