AMSTERDAM, NETHERLANDS / RankWire.AI / – A medication traditionally used for high blood pressure has demonstrated promising results in decelerating vanishing white matter disease in children. Researchers at Amsterdam UMC evaluated guanabenz in a group of 33 children diagnosed with this rare inherited neurological condition. The study compared these patients with 66 closely matched cases from an international historical registry. Findings linked the treatment to 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, causes damage to the brain’s white matter, often beginning in childhood. Diagnosis was confirmed through genetic testing and magnetic resonance imaging for children enrolled in the trial. These participants exhibited symptoms by age six and had lived with the condition for no more than eight years. Prior to the study, all children could walk at least 10 steps with limited support. Eligible patients were enrolled from May 2021 to May 2024.
The primary focus of the analysis was the duration of ability to walk with assistance. Each treated child was matched with two untreated historical controls based on disease onset and level of disability. The hazard ratio for reaching the study’s primary walking endpoint was 0.33, indicating a 67% reduction in risk for children receiving guanabenz. Brain imaging also revealed less white matter deterioration among treated participants, with some children showing no detectable progression during the follow-up period.
Study monitors walking ability and brain tissue changes
Participants took guanabenz orally, starting at 0.15 milligrams per kilogram of body weight daily. Doses were gradually increased over approximately six weeks based on each child’s tolerance. The trial identified 2 milligrams per kilogram daily as the optimal dose. Out of 33 enrolled children, 31 completed the study, with a median treatment duration of 3.1 years. The most notable effects were observed in children whose symptoms began at age three or later.
Throughout the trial, 63 serious adverse events were documented among 25 participants. Of these, investigators judged 30 to be likely or very likely linked to guanabenz. Hallucinations occurred in 18 children, primarily within the first four months of treatment. Severe constipation affected three children, and one experienced temporary low blood pressure accompanied by sedation. All these adverse events resulted in brief hospital stays and later resolved. No participant discontinued treatment due to side effects, and no deaths occurred during the trial.
Extended research ongoing following phase 1/2 trial
The trial lacked random assignment; instead, researchers compared guanabenz-treated children with historical patients from the Vanishing White Matter Registry. Consequently, there was no contemporaneous untreated control group. The study team emphasizes the importance of longer follow-up to verify the potential disease-modifying effects of guanabenz. It is important to note that guanabenz does not cure VWM, nor has it been approved by regulators as a treatment for the disorder.
Amsterdam UMC continues follow-up studies involving children from the initial trial. This extension aims to assess long-term effects on walking ability, neurological function, brain imaging, safety, and different doses of guanabenz. Currently, the drug remains available for VWM only in a research setting. Originally developed for hypertension, guanabenz targets cellular stress pathways associated with the disease. These new findings offer valuable clinical data regarding treatment effects in children with early-onset vanishing white matter disease.