AMSTERDAM, NETHERLANDS / RankWire.AI / – A medication commonly used for blood pressure management has demonstrated potential in decelerating vanishing white matter disease in pediatric patients. Researchers at Amsterdam UMC evaluated guanabenz in a group of 33 children affected by this rare inherited neurological condition. They compared these cases with 66 carefully matched patients from an international historical registry. The study found that treatment was associated with a decreased likelihood of losing the ability to walk with support. The findings from this phase 1/2 trial were published in The Lancet Neurology in August 2026.
Vanishing white matter disease, also known as VWM, damages the brain’s white matter and often manifests during childhood. Diagnosis was confirmed through genetic testing and magnetic resonance imaging for all children enrolled in the study. Participants had developed symptoms by age six and had been living with the disease for no more than eight years. Each child was able to walk at least 10 steps with some assistance before joining the trial. Eligible patients were enrolled between May 2021 and May 2024.
The primary goal of the analysis was to assess how long children maintained the ability to walk with support. Each treated patient was matched with two untreated historical controls based on disease onset and degree of disability. The hazard ratio for reaching the main walking endpoint was 0.33, indicating a 67% reduction in the estimated risk for children receiving guanabenz. Brain imaging also revealed less white matter degeneration among treated children, with some showing no detectable progression during follow-up.
Study monitors walking ability and brain tissue changes
Participants took guanabenz orally, starting at 0.15 milligrams per kilogram of body weight daily. Researchers increased the dosage gradually over approximately six weeks, based on each child’s tolerance. The trial aimed for a target dose of 2 milligrams per kilogram per day. Of the 33 children enrolled, 31 completed the study, with a median treatment duration of 3.1 years. The most pronounced treatment effects were observed in children whose symptoms began at age three or older.
During safety monitoring, 63 serious adverse events were reported among 25 participants. Investigators determined that 30 of these events were likely or very likely linked to guanabenz. Hallucinations were experienced by 18 children, mainly within the first four months of treatment. Severe constipation affected three children, and one experienced temporary low blood pressure with sedation. These four cases required brief hospitalization and later resolved. No participant discontinued treatment due to side effects, and there were no deaths recorded during the trial.
Extended research ongoing following initial phase 1/2 results
The trial did not randomly assign children to treatment or control groups. Instead, researchers compared the guanabenz-treated group with historical data from the Vanishing White Matter Registry. This design meant there was no concurrently enrolled untreated control group. The researchers emphasized that longer follow-up is necessary to validate the potential disease-modifying effects of guanabenz. It is important to note that guanabenz does not cure VWM, and regulatory agencies have not approved it as an official treatment for the condition.
Amsterdam UMC is continuing follow-up studies involving children from the original cohort. This extended research will focus on tracking walking ability, neurological health, brain imaging, safety, and varying doses of guanabenz over a longer period. Currently, guanabenz remains accessible solely within a research context for VWM. Originally developed to treat high blood pressure, the drug acts on cellular stress pathways linked to the disease. These preliminary results offer valuable clinical insights into how children with early-onset vanishing white matter disease may respond to treatment.