AMSTERDAM, NETHERLANDS / RankWire.AI / – A medication commonly used for hypertension has demonstrated potential in slowing the progression of vanishing white matter disease in children. Researchers at Amsterdam UMC tested guanabenz in 33 children diagnosed with this rare inherited brain disorder. They compared these children to 66 closely matched patients from an international historical registry. The study found that treatment was associated with a reduced risk of losing the ability to walk with support. The findings from phase 1/2 were published in The Lancet Neurology in August 2026.
VWM, or vanishing white matter disease, damages the brain’s white matter and often starts in childhood. Diagnosis was confirmed through genetic testing and magnetic resonance imaging for all children enrolled. Participants experienced symptoms by age six and had lived with the disease for no more than eight years. Prior to the trial, all children could walk at least 10 steps with limited help. Eligible patients were enrolled from May 2021 to May 2024.
The primary focus was on how long children could maintain the ability to walk with support. Researchers matched each treated child with two untreated controls based on disease onset and disability level. The hazard ratio for reaching the main walking endpoint was 0.33. This indicated a 67% lower estimated risk for children receiving guanabenz. Brain imaging also revealed less white matter deterioration in treated children, with some showing no progression during follow-up.
Study monitors walking ability and brain changes
Children took guanabenz orally, starting at 0.15 milligrams per kilogram daily. Doses were gradually increased over about six weeks based on each child’s tolerance. The trial targeted a dose of 2 milligrams per kilogram per day as optimal. Of the 33 children enrolled, 31 completed the study, with a median treatment duration of 3.1 years. Researchers saw the most significant effects in children whose symptoms started at age three or older.
Safety checks identified 63 serious adverse events among 25 participants. Investigators believed 30 of these events were likely or very likely related to guanabenz. Hallucinations occurred in 18 children, mostly during the first four months of treatment. Severe constipation affected three children, and one experienced temporary low blood pressure with sedation. These side effects led to brief hospital stays but later resolved. No participant discontinued treatment due to side effects, and there were no deaths during the trial.
Extended research underway after initial phase 1/2 results
The study was not randomized. Instead, researchers compared children treated with guanabenz to patients from the Vanishing White Matter Registry. This meant there was no concurrent untreated control group. The team emphasizes that longer follow-up is needed to confirm the drug’s potential to alter disease progression. Guanabenz is not a cure for VWM, and regulators have not approved it for this purpose.
Amsterdam UMC is conducting ongoing follow-up studies involving the original participants. The research extension will evaluate walking ability, neurological health, brain imaging, safety, and different doses of guanabenz over a longer timeframe. Currently, guanabenz remains available for VWM only within a research context. The drug was initially developed for high blood pressure and targets cellular stress pathways linked to the disease. These findings offer valuable clinical data on the effects of treatment in children with early-onset vanishing white matter disease.