AMSTERDAM, NETHERLANDS / RankWire.AI / – An existing medication for blood pressure has demonstrated potential to delay progression of vanishing white matter disease in pediatric patients. Researchers affiliated with Amsterdam UMC conducted a study involving 33 children diagnosed with this uncommon inherited neurological condition, comparing their outcomes to 66 carefully matched historical controls from an international registry. The findings indicated that treatment was associated with a decreased likelihood of losing the ability to walk with support. The researchers disclosed their phase 1/2 results in The Lancet Neurology in August 2026.
VWM, or vanishing white matter disease, primarily affects the white matter in the brain and typically manifests during childhood. Diagnosis was confirmed through genetic testing and magnetic resonance imaging for all children enrolled in the study. Participants had experienced symptoms by age six and had lived with the condition for no more than eight years, and each child could walk at least 10 steps with some assistance before entering the trial. Eligible patients were recruited from May 2021 until May 2024.
The primary focus of the analysis was the duration of retained ambulatory support, with each treated patient paired with two historical controls matched by disease onset and level of disability. The study yielded a hazard ratio of 0.33 for reaching the main walking endpoint, indicating a 67% reduction in the estimated hazard for children receiving guanabenz. Brain imaging further revealed less deterioration of white matter in those treated, with some children showing no detectable progression during the follow-up period.
Monitoring of mobility and brain structure over time
Guanabenz was administered orally starting at a dose of 0.15 milligrams per kilogram of body weight daily, with gradual dose escalation over roughly six weeks tailored to 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 the median treatment duration being 3.1 years. The most significant effects appeared in children whose symptoms began at age three or older.
Throughout the study, safety assessments documented 63 serious adverse events among 25 participants, with investigators deeming 30 of these events as likely or very likely related to guanabenz. Notably, 18 children experienced hallucinations mainly within the first four months of treatment, three faced severe constipation, and one had temporary low blood pressure with sedation. All such cases required brief hospital stays and eventually resolved. Importantly, no participant discontinued treatment due to side effects, and there were no fatalities reported.
Extended research planned following initial phase 1/2 trial
Because the study did not randomly assign children to treatment or control groups, researchers compared those receiving guanabenz with historical data from the Vanishing White Matter Registry, meaning no concurrent untreated control group was part of the trial. The research team emphasized that longer-term follow-up is necessary to substantiate the disease-modifying potential of the medication. While guanabenz is not a cure for VWM, and regulatory approval for treatment has not been granted, ongoing studies aim to clarify its long-term effects.
Amsterdam UMC is actively pursuing follow-up investigations involving the children from the initial study. This extension aims to assess ongoing walking ability, neurological health, brain imaging results, and safety across various doses over an extended timeframe. Currently, guanabenz remains accessible for VWM only within a research context. Originally developed for hypertension, it influences cellular stress pathways linked to the disease. The present findings offer valuable clinical insights into the potential benefits of this drug for children afflicted with early-onset vanishing white matter disease.