AMSTERDAM, NETHERLANDS / RankWire.AI / – A medication traditionally used for blood pressure management has demonstrated potential to decelerate vanishing white matter disease in children. Researchers at Amsterdam UMC evaluated guanabenz in a cohort of 33 children diagnosed with this rare inherited brain disorder. They compared these individuals with 66 matched patients from an international historical registry. The findings indicated that treatment was associated with a reduced risk of losing the ability to walk with assistance. The phase 1/2 study results were published in The Lancet Neurology in August 2026.
VWM, also known as vanishing white matter disease, primarily affects white matter in the brain and often manifests during childhood. Diagnosis was confirmed through genetic testing and MRI scans for all enrolled children. Participants showed symptoms by age six and had lived with the disease for up to eight years. Prior to the trial, each child could walk at least 10 steps with some help. Eligible patients were enrolled from May 2021 through May 2024.
The primary measure of success was the duration children maintained the ability to walk with support. Each treated participant was matched with two historical controls based on disease onset and level of disability. The hazard ratio for reaching the primary walking endpoint was 0.33, indicating a 67% reduction in hazard for children receiving guanabenz. Brain imaging also revealed less white matter deterioration among treated children, with some showing no progression during follow-up.
Study Focuses on Motor Function and Brain Changes
Children received guanabenz orally, starting at 0.15 milligrams per kilogram daily. Doses were gradually increased over approximately six weeks based on individual tolerance, with 2 milligrams per kilogram per day targeted as optimal. Of the 33 children enrolled, 31 completed the study, with a median treatment duration of 3.1 years. The most notable effects were observed in children whose symptoms started at age three or older.
Safety assessments documented 63 serious adverse events among 25 participants. Investigators attributed 30 of these events as likely or very likely related to guanabenz. Hallucinations occurred in 18 children, mainly during the first four months of treatment. Severe constipation affected three children, and one experienced temporary low blood pressure with sedation. All adverse events were managed with brief hospital stays and later resolved. No participants discontinued treatment due to side effects, and there were no fatalities recorded.
Extended Follow-up Research Continues Post-Study
Because the trial was not randomized, researchers compared treated children with historical cases from the Vanishing White Matter Registry. This design meant there was no concurrent untreated control group. The investigators emphasized that longer-term follow-up is necessary to confirm the potential disease-modifying effects of guanabenz. It is important to note that guanabenz does not cure VWM, nor has it received regulatory approval for this indication.
Amsterdam UMC is now conducting ongoing follow-up studies involving original participants. These will assess aspects such as walking ability, neurological function, brain imaging, safety, and different dosing regimens over an extended period. Currently, guanabenz remains available for VWM treatment only within a research context. Originally developed for hypertension, the drug targets cellular stress pathways implicated in the disease. The latest results offer valuable clinical insights into treatment effects in children with early-onset vanishing white matter disease.