AMSTERDAM, NETHERLANDS / RankWire.AI / – An existing medication for blood pressure has demonstrated evidence of decelerating vanishing white matter disease in pediatric patients. Researchers at Amsterdam UMC evaluated guanabenz in a cohort of 33 children diagnosed with this rare inherited brain disorder. They compared these participants with 66 carefully matched patients sourced from an international historical registry. The findings indicated that treatment was associated with a reduced risk of losing the ability to walk with support. The researchers published the phase 1/2 results in The Lancet Neurology in August 2026.
Vanishing white matter disease, also known as VWM, affects the brain’s white matter and typically manifests during childhood. Diagnosis was confirmed through genetic testing and magnetic resonance imaging for children enrolled in the trial. Participants had experienced symptoms by age six and had been living with the disease for no more than eight years. Prior to the study, each child could walk at least 10 steps with limited assistance. Eligible patients were enrolled from May 2021 to May 2024.
The primary endpoint centered on the duration children maintained the ability to walk with support. For each treated patient, researchers matched two untreated controls from historical data based on disease onset and level of disability. The hazard ratio for reaching the main walking endpoint was 0.33, indicating a 67% lower estimated risk for children treated with guanabenz. Brain imaging also revealed less white matter deterioration among treated children, with some showing no detectable progression during follow-up.
Study Monitors Walking Capacity and Brain Structural Changes
Participants received guanabenz orally, beginning at a dose of 0.15 milligrams per kilogram of body weight daily. Doses were gradually increased over approximately six weeks based on individual tolerance. The trial aimed for an optimal dose of 2 milligrams per kilogram per day. Out of the 33 children enrolled, 31 completed the study, with a median treatment duration of 3.1 years. The strongest effects were observed among children whose symptoms started at age three or older.
Throughout the trial, safety assessments identified 63 serious adverse events among 25 participants. Of these, investigators considered 30 likely or very likely related to guanabenz. Hallucinations were reported in 18 children, predominantly within the first four months of treatment. Severe constipation affected three children, while one experienced temporary hypotension with sedation. These four cases required brief hospitalization and later resolved. No participant withdrew from treatment due to side effects, and there were no deaths recorded during the study.
Extended Follow-Up Research Continues Beyond Phase 1/2 Results
Because the study did not randomly assign children to treatment or control groups, researchers relied on comparisons with historical patients from the Vanishing White Matter Registry. This design meant there was no concurrent untreated control group. The researchers emphasized that longer-term follow-up is necessary to verify the potential disease-modifying effects of guanabenz. It is important to note that guanabenz does not cure VWM, and it has not been approved as a formal treatment by regulators.
Amsterdam UMC is planning ongoing follow-up studies involving children from the initial cohort. This extension aims to assess walking ability, neurological function, brain imaging, safety, and different dosing strategies over an extended period. Currently, guanabenz remains available solely within research settings for VWM. Originally developed for hypertension, it acts on cellular stress pathways associated with the disease. The present findings provide valuable clinical data on the effects of treatment in children with early-onset vanishing white matter disease.