Has science FINALLY found a cure for Wiskott–Aldrich syndrome? All you need to know- The Week

Back in 1937, Dr Alfred Wiskott, a World War I veteran who later became a physician, described a family in which three brothers had eczema, hematochezia, and recurrent ear infections from early infancy. Wiskott noted that while all three boys died young due to bleeding and infection, their sisters remained healthy. He proposed that the disease stemmed from a platelet defect and named it “hereditary thrombopathia.”

Seventeen years later, Dr Robert Aldrich, an American paediatrician, studied six generations of a Dutch family affected by the same conditions. He found that while several males had died due to the disease, no female was affected, and he proposed that the disorder had an X-linked recessive inheritance pattern. By the 1960s, such patients were being increasingly recognised, and the condition came to be known as Wiskott–Aldrich syndrome.

In 1968, the first bone marrow transplant using a matched unrelated donor was successfully performed on a patient with WAS. This disease spurred some of the earliest interest in bone marrow transplantation as a potential cure for immunodeficiency disorders.

In 1994, the gene causing the disease was identified on the X chromosome by Dr. Uta Francke. Since then, much of the focus has been on developing gene therapy as an alternative to bone marrow transplantation. And, on December 9, the U.S. Food and Drug Administration approved Waskyra, the first cell-based gene therapy for the treatment of WAS.

WAS affects almost exclusively males. Today, about 1 in 250,000 live male births are identified with this rare disease. Until now, the primary treatment options have been supportive therapies aimed at managing and preventing clinical manifestations. The only potentially curative approach—hematopoietic stem cell transplantation—required a compatible donor, which was not always available, and carried significant risks. Waskyra is changing that scenario.

Dr Vinay Prasad, Chief Medical and Scientific Officer and Director of the FDA’s Center for Biologics Evaluation and Research, noted that this gene therapy uses the patient’s own genetically corrected hematopoietic stem cells to treat the disease. Waskyra is made from a patient’s own blood-forming stem cells, which are genetically modified to carry working copies of the WAS gene. After the patient receives mild conditioning treatment, these corrected cells are infused back into the bloodstream, where they rebuild the blood system. This restores normal WAS protein levels and addresses the root cause of the disease.

This unique therapy was developed through decades of research at the San Raffaele Telethon Institute for Gene Therapy. Following the FDA approval, Ilaria Villa, CEO of Fondazione Telethon, said that the authorisation of Waskyra is an extraordinary achievement for the global rare disease community.

Its safety and effectiveness were evaluated in two open-label, single-arm international studies and an expanded access program involving 27 patients with severe WAS. The results showed strong and sustained clinical improvement, with major reductions in the symptoms that typically drive illness and mortality. Severe infections decreased by 93 per cent in the 6–18 months following treatment compared to the year before. Moderate and severe bleeding episodes fell by 60 per cent in the first year after treatment, and most patients reported no moderate or severe bleeding at all four years later.