AMSTERDAM, NETHERLANDS / RankWire.AI / – An established medication for high blood pressure has demonstrated potential in decelerating the progression of vanishing white matter disease in pediatric patients. Researchers at Amsterdam UMC conducted a trial involving guanabenz administered to 33 children diagnosed with this rare inherited neurological condition. Their outcomes were compared against 66 closely matched cases from an international historical registry. Results indicated that treatment was associated with a decreased risk of losing the ability to walk with support. The findings from this phase 1/2 study were published in The Lancet Neurology in August 2026.
Vanishing white matter disease, also known as VWM, primarily affects the brain’s white matter, often manifesting during childhood. Diagnostic confirmation was obtained through genetic testing and magnetic resonance imaging in children enrolled in the trial. Participants exhibited symptoms by the age of six and had been living with the disease for no more than eight years. All children could walk at least ten steps with some assistance before entering the study. Eligible patients were enrolled from May 2021 to May 2024.
The primary endpoint centered on how long children retained the ability to walk with support. To assess this, each treated patient was matched with two untreated historical controls based on disease onset and severity. The hazard ratio for reaching the primary walking endpoint was calculated at 0.33, suggesting a 67% lower estimated risk for children treated with guanabenz. Additionally, brain imaging revealed less deterioration of white matter in those receiving treatment, with some children showing no progression over the follow-up period.
Study monitors walking capacity and brain tissue changes
Participants received guanabenz orally, starting at a dose of 0.15 milligrams per kilogram of body weight daily. The dosage was gradually increased over approximately six weeks, tailored to each child’s tolerance. The trial identified 2 milligrams per kilogram per day as the optimal dose. Out of 33 enrolled children, 31 completed the study, with a median treatment duration of 3.1 years. The most pronounced effects were observed in children whose symptoms began at age three or older.
Throughout the trial, safety assessments recorded 63 serious adverse events among 25 participants. Investigators believed 30 of these events were probably or very likely related to guanabenz. Hallucinations were reported in 18 children, mostly within the first four months of treatment. Severe constipation affected three children, and one experienced transient hypotension with sedation. These episodes required brief hospitalization but ultimately resolved. No participants discontinued treatment due to side effects, and no fatalities occurred during the trial.
Extended follow-up research underway post phase 1/2 trial
The study design did not include random assignment of children to treatment or control groups. Instead, guanabenz-treated patients were compared with historical data from the Vanishing White Matter Registry. Consequently, there was no concurrent untreated control group. Researchers emphasized that longer-term follow-up is necessary to verify the disease-modifying potential of the drug. It is important to note that guanabenz does not cure VWM, and regulatory agencies have not approved it as a treatment for the condition.
Amsterdam UMC is continuing longitudinal research involving participants from the initial study. This extension aims to evaluate walking ability, neurological function, brain imaging, safety concerns, and varying doses of guanabenz over an extended period. Currently, guanabenz remains accessible only within research settings for VWM. Originally developed for high blood pressure, it acts on cellular stress pathways that are implicated in the disease. The recent findings offer valuable clinical data regarding treatment effects in children with early-onset vanishing white matter disease.