A groundbreaking gene therapy for Wiskott-Aldrich Syndrome has received a positive regulatory opinion from European authorities, marking a milestone achievement after decades of research at the San Raffaele Telethon Institute for Gene Therapy in Milan, according to News-Medical. The therapy, called Waskyra™, represents the culmination of a 20-year scientific journey to develop life-saving treatments for rare genetic disorders that affect children worldwide.
Revolutionary Treatment for Ultra-Rare Condition
Wiskott-Aldrich Syndrome affects an estimated 1 in 250,000 live male births, making it one of the rarest genetic disorders, according to News-Medical. The condition is a life-threatening primary immunodeficiency that leaves children vulnerable to severe infections, bleeding disorders, and increased cancer risk. Until now, treatment options have been limited to bone marrow transplantation, which often carries serious side effects and requires tissue-matched donors that more than 80 percent of patients lack, according to Stjude.
The newly approved therapy uses an innovative ex vivo gene therapy approach, where stem cells are taken from the patient's bone marrow, genetically corrected in the laboratory, and then returned to the patient. This technique sidesteps many of the risks associated with traditional treatments while providing a potential cure for the underlying genetic defect.
Decades of Persistent Research Pay Off
The path to this breakthrough exemplifies the long journey typical of medical research breakthroughs. According to Stjude, researchers have worked for more than 20 years to develop gene therapy treatments for rare immunodeficiencies, building on research that began with X-linked severe combined immunodeficiency (SCID-X1), sometimes called "bubble boy" disease. The late Brian Sorrentino, MD, Experimental Hematology director at St. Jude, dedicated his career to finding cures for these immune disorders, understanding firsthand the urgency of treating childhood diseases.
The San Raffaele Telethon Institute for Gene Therapy, established since 1995 as a joint venture between Fondazione Telethon and Fondazione San Raffaele, has been at the forefront of this research, according to Gsk. Clinical trials for Wiskott-Aldrich Syndrome and metachromatic leukodystrophy were initiated at HSR-TIGET last spring and are currently recruiting patients.
Strategic Industry Partnerships Accelerate Development
The success of this gene therapy reflects strategic collaborations between academic institutions and pharmaceutical companies. GlaxoSmithKline PLC has formed alliances with Fondazione Telethon and Fondazione San Raffaele to research and develop novel treatments for rare genetic disorders, according to Gsk. Under these agreements, GSK gained exclusive licenses to develop treatments for conditions like ADA Severe Combined Immune Deficiency, which affects approximately 350 children worldwide.
Fondazione Telethon will receive an upfront 10 million euro payment from GSK as part of these collaborative arrangements, according to the extracted facts. The partnership capitalizes on research performed at HSR-TIGET and represents a new model for bringing academic discoveries to patients through industry partnerships.
Overcoming Technical Challenges in Gene Therapy
Developing effective gene therapies requires overcoming significant technical hurdles. According to Genethon, 40% of patients are naturally immune to certain vectors used in gene therapy, limiting treatment options. Additionally, the maximum capacity of one AAV (Adeno-Associated Virus) vector is 4.5 kilobase pairs, which restricts the size of genes that can be delivered.
To address these challenges, researchers are developing next-generation technologies. Genethon, with its 30-year history as a gene therapy research organization, is working on dual AAV vectors that increase packing capacity for delivering larger genes, according to Genethon. The organization is also applying artificial intelligence to create more efficient AAV capsids that better target specific tissues while reducing adverse effects.
Broader Impact on Rare Disease Treatment
The approval of Waskyra™ represents more than a single therapeutic success—it demonstrates a new paradigm for rare disease research. "This milestone demonstrates that academic research, when guided by a strong sense of responsibility towards patients and conducted to the highest industrial standards, can truly change the natural history of rare diseases," said Ilaria Villa, General Director of Fondazione Telethon, according to News-Medical.
Phase I/II studies have demonstrated the potential of ex vivo gene therapy to restore long-term immune function and protect against severe infections in children with genetic immunodeficiencies, according to Gsk. All of the disorders being targeted have molecular mechanisms that are well understood and are caused by faults in a single gene, making them ideal candidates for gene therapy approaches.
Looking Toward the Future
The timing of this breakthrough is particularly significant as it coincides with Rare Disease Day on February 28, 2025, according to Genethon. The approval comes as the field of gene therapy is experiencing rapid advancement, with new technologies promising safer, more effective, and lower-cost treatments that could expand access to these life-saving medicines.
Fondazione Telethon has achieved the distinction of being the first non-profit organization to successfully lead the full pathway from laboratory research to regulatory approval, according to News-Medical. The therapy will be made available to patients at IRCCS Ospedale San Raffaele, a recognized center of excellence in gene therapy, where the clinical trial phase was conducted. Meanwhile, the BLA for the same gene therapy remains under review by the U.S. Food and Drug Administration.
"Making therapies truly available is essential to offering families a real chance at treatment. The true meaning of science lies in the impact it has on people's lives," added Dr. Alessandro Aiuti, Deputy director clinical research at SR-Tiget, according to News-Medical. This sentiment captures the ultimate goal of the decades-long research effort: transforming scientific discovery into hope for children and families facing rare genetic disorders.