Hurler syndrome (mucopolysaccharidosis type I) is caused by absent α-l-iduronidase (IDUA) expression due to autosomal recessively inherited mutations in the IDUA gene, leading to accumulation of glycosaminoglycans (GAGs). Enzyme replacement therapy with laronidase reduces somatic symptoms but the enzyme does not cross the blood–brain barrier. Until now, definitive treatment has been allogeneic haematopoietic cell transplantation, which requires an HLA-matched donor and immunosuppression. An Italian group now reports eight patients, mean age 1.9 (standard deviation 0.5) years, with Hurler syndrome who lacked a donor, had an IQ >70 and were treated with autologous haematopoietic stem and progenitor cell gene therapy.1 The researchers used a lentivirus vector expressing IDUA, with a strong promoter resulting in supraphysiological IDUA levels, greater than those seen with allogeneic haematopoietic cell transplantation. At follow-up after a median of 2.1 years, high IDUA levels persisted, including being detectable in the CSF associated with local clearance of GAGs, and urinary GAG excretion fell to normal in four of five patients evaluated. Magnetic resonance imaging of brain and spine was stable or improved. The patients' cognitive ability was stable, motor development continued, joint stiffness reduced and growth was normal. While these results are encouraging, an accompanying editorial stressed limitations including short-term follow-up and the need for immunosuppression to allow the gene-corrected product to be delivered to the patient's marrow.2