A single infusion of genetically corrected autologous hematopoietic stem cells can provide durable clinical benefit for patients with Wiskott-Aldrich Syndrome, a rare genetic disorder that impairs immune function and platelets function, exposing affected children from an early age to severe infections, bleeding episodes, eczema and autoimmune complications.
These findings are reported in a paper published in the New England Journal of Medicine and authored by Professor Alessandro Aiuti , Head of Pediatric Immunohematology at IRCCS Ospedale San Raffaele, Deputy Director of the San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget), Professor of Pediatrics at Vita-Salute San Raffaele University, and the study’s senior and corresponding author. The publication presents the outcomes of 27 patients treated with etuvetidigene autotemcel (etu-cel) , an autologous gene therapy developed to correct the genetic defect underlying the disease. Patients were followed for at least 5.7 years, with some monitored for more than 13 years. Overall survival was 96% at both one and five years , while severe infections and moderate-to-severe bleeding events were markedly reduced following treatment. Among the adverse events observed, none were attributable to the gene therapy product, confirming a favorable risk-benefit profile.
The program originated and was developed within SR-Tiget , established in 1996 through a partnership between IRCCS Ospedale San Raffaele and Fondazione Telethon to develop gene therapies for rare genetic diseases, together with the Pediatric Immunohematology and Bone Marrow Transplant Unit of IRCCS Ospedale San Raffaele . These institutions played a central role in developing the therapeutic approach, providing clinical care to patients and conducting their long-term follow-up. Between December 2025 and January 2026, Fondazione Telethon obtained marketing authorization for this gene therapy in both the European Union and the United States.
Wiskott-Aldrich Syndrome: a Rare Disease Affecting the Immune System and Platelets
Wiskott-Aldrich syndrome is a rare X-linked genetic disorder, caused by mutations in the WAS gene, which encodes the WASP protein, a key regulator of blood cells and immune system function. The disease has an incidence of approximately 4 cases per million live births, almost exclusively males, while females are typically healthy carriers.
The condition generally manifests within the first months of life with a combination of clinical features, including thrombocytopenia with reduced platelet volume, frequent and potentially life-threatening bleeding episodes, recurrent and/or severe infections, eczema, autoimmune and autoinflammatory manifestations, and an increased risk of blood cancers. Supportive treatments such as immunoglobulin replacement, antimicrobials, platelet transfusions and immunosuppressive drugs may help manage some complications but do not address the genetic cause of the disease. Allogeneic hematopoietic stem cell transplantation can be curative, but its success depends on the availability of a suitable donor and carries significant risks, including infections, transplant rejection, graft failure and graft-versus-host disease.
The SR-Tiget Gene Therapy
The gene therapy described in the publication is based on an autologous approach . Hematopoietic stem cells are collected from the patient, genetically corrected in the laboratory using a lentiviral vector carrying a functional copy of the WAS gene, and reinfused into the patient following reduced-intensity conditioning chemotherapy. The goal is to enable long-term production of blood and immune cells capable of expressing the WASP protein, which is defective in patients with Wiskott-Aldrich syndrome.
The article published in the New England Journal of Medicine integrates data from two prospective clinical trials and an expanded-access program. In total, 27 patients were treated at a median age of 2.6 years and followed for a minimum of 5.7 years, with some observed for more than 13 years. The results show 96% survival at 1 and 5 years and a sustained reduction in the major complications of the disease. Severe infections and moderate-to-severe bleeding events declined substantially after treatment and clinical benefits were maintained over time.
Patients also demonstrated stable engraftment of genetically corrected cells , progressive restoration of WASP protein expression in immune cells and platelets, and improved immune function . At the latest follow-up, all patients had discontinued immunoglobulin replacement therapy. Three years after treatment, all patients had left protected environments; more than 80% were attending school or kindergarten, and approximately half were participating in sports activities. The most common adverse event of grade 3 or higher registered was central venous catheter–related infection, and no evidence of insertional oncogenesis was observed. None of the adverse reactions observed in clinical trials were attributable to the gene therapy itself (for complete safety details, please refer to the official approved Product Information ).
“These results represent an important milestone in the history of gene therapy for Wiskott-Aldrich Syndrome. Long-term follow-up shows that a single infusion of genetically corrected hematopoietic stem cells can provide sustained clinical benefit, reducing complications that profoundly affect the lives of patients and their families and thereby improving quality of life,” said Francesca Ferrua , pediatrician at the Pediatric Immunohematology Unit of IRCCS Ospedale San Raffaele and the Clinical Unit of SR-Tiget, and first author of the study.
The results of years of research and future perspectives
This paper marks another milestone in a research journey that began more than twenty years ago at SR-Tiget. Following the first clinical results published in Science in 2013 and interim data reported in The Lancet Haematology in 2019, the study confirms the value of a program originating from academic research and advanced through close collaboration between laboratory science, clinical medicine and translational development. Between December 2025 and January 2026 , this journey also led to the approval of etuvetidigene autotemcel (Waskyra ® ) by both the U.S. Food and Drug Administration (FDA) and the European Commission , following a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP).
The therapy was initially developed with contributions from industrial partners, including GlaxoSmithKline and Orchard Therapeutics, and was subsequently reacquired and brought to approval by Fondazione Telethon , which now holds ownership of the therapy under a non-profit model aimed at ensuring continued development and access to gene therapies for ultra-rare diseases.
“Looking to the future, this experience points to a possible pathway for making advanced therapies available even for diseases so rare that they risk being excluded from traditional pharmaceutical development models,” added Professor Alessandro Aiuti . “For families living with Wiskott-Aldrich syndrome, and for many other patient communities still lacking a cure, the path pursued at SR-Tiget in Milan demonstrates how research can become a tangible opportunity when scientific innovation, clinical care and responsibility towards patients remain part of the same project.”
For more information about the therapy, please refer to the official documentation available on the websites of the U.S. Food and Drug Administration ( FDA ) and the European medicines Agency ( EMA ).
Randomized controlled/clinical trial
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Etuvetidigene Autotemcel for the Treatment of Wiskott-Aldrich Syndrome
23-Sep-2026