April 2026 Research Update

This month included a single-patient, first-in-human report that adds an early signal that targeting the brain and spinal fluid with gene therapy might be feasible in severe Hurler syndrome, at least for one child. Over more than 5 years, the treatment was reported as well tolerated, brain imaging stayed normal, and development progressed beyond what would be expected in untransplanted Hurler syndrome. This is encouraging as a research direction, but it is still too early to know how often similar results would happen in other children. [1]

In this report, the child received intracisternal RGX-111 (a gene therapy designed to deliver the IDUA gene) and continued weekly IDUA infusions, without receiving a stem cell transplant. The authors reported mild, self-limiting side effects and noted that cognitive, speech, and motor skills still remained below typical averages by about 1 to 2 standard deviations, even as progress continued. Taken together, the report suggests possible benefit for brain-related aspects of Hurler syndrome while also showing that development did not become fully typical. [1]

For patients and caregivers, this mainly matters as early research that helps clarify what CNS-directed (brain-targeted) gene therapy might look like in real life, including long follow-up. It does not establish what outcomes most children would have, because it is one patient and there was no comparison group. What becomes clearer is that long-term monitoring can be done and that mild short-term side effects and stable brain imaging were reported in this child, while questions about predictability and who might benefit remain unanswered. [1]

Studies published this month add clarity that hand tendon problems like trigger digits are common in children with MPS I and can still reflect ongoing storage in tissues, even after stem cell transplant. In a group of children followed at one center, trigger digits affected many patients and sometimes came back after surgical release. Tissue samples from the finger pulley often showed storage-related cells, suggesting that local hand tissues may not fully normalize. [2]

In this retrospective study of 33 children with MPS I, 39% had trigger digits, with a total of 61 affected digits and diagnosis around early childhood. Surgical release was performed in 11 patients, and recurrence was reported in 2 cases. When pulley tissue was examined, foam cell macrophages were seen in 5 of 6 evaluated patients despite successful HSCT, which helps explain why hand problems can persist over time. [2]

This information may matter now because trigger digits can affect comfort and hand function, and the study helps set expectations that these problems can be relatively frequent in MPS I. It also helps clarify why symptoms can continue even after major disease treatments, since local tissues may still show signs of storage. What remains uncertain is how often recurrence happens in other settings and which factors (like age, severity, or treatment history) best predict who will develop trigger digits, because this report comes from a single center and does not test prevention strategies. [2]

This month also added a large, real-world view of newborn screening that highlights a key issue for MPS I screening: early test positives do not always mean a baby truly has MPS I. In a 10-year program in Tuscany, there were multiple initial positive screens for MPS I but no confirmed cases after follow-up testing. The study puts a spotlight on pseudodeficiency and uncertain gene changes as practical challenges that families and programs may face after an abnormal screen. [3]

Across 234,642 screened newborns, 45 babies initially screened positive for MPS I, yet none were confirmed after repeat testing. The program also reported finding 10 previously unreported IDUA gene variants during confirmatory workups, alongside a broader burden of pseudodeficiency in a multiethnic population. This helps explain why strong second-step testing is important, because the first screen can flag babies who do not go on to have confirmed MPS I. [3]

For families, this mainly matters for understanding what an abnormal newborn screen can and cannot tell you right away. This study supports the idea that initial MPS I screening results can create uncertainty and that confirmatory testing is essential before a diagnosis is established. What becomes clearer is that false positives and unclear genetic findings are a real part of screening programs, while the study does not answer how the best follow-up process should be designed in every region or population. [3]