AMSTERDAM, NETHERLANDS / RankWire.AI / – Researchers at Amsterdam UMC have found that guanabenz, an older medication used for blood pressure, might slow the progression of vanishing white matter disease in children. In a phase 1/2 trial, 33 ambulatory children were observed and their results were compared with 66 matched historical controls. The study revealed a significantly decreased risk of losing the ability to walk with support among those treated with guanabenz. Researchers shared the findings in The Lancet Neurology in August 2026. Vanishing white matter disease, or VWM, is a rare inherited neurodegenerative condition that typically manifests in early childhood.
Children included in the trial had a confirmed VWM diagnosis through genetic testing and magnetic resonance imaging. Eligibility criteria required disease onset at age six or younger and a disease duration of no more than eight years. They also needed to walk at least 10 steps with no more than light support from one hand. Between May 31, 2021, and May 31, 2024, researchers enrolled 33 eligible patients, of whom 31 completed the trial. The median age was 5.4 years, and the median treatment duration was 3.1 years.
The primary measure of effectiveness was the loss of walking ability with support. Each treated child was matched with two historical controls based on disease onset and disability. The analysis yielded a hazard ratio of 0.33 for reaching the main walking endpoint, indicating a 67% lower estimated hazard among treated children. Brain scans also demonstrated less deterioration of white matter in the treated group, with some showing no detectable progression. The strongest treatment effect appeared in children whose disease started at age three or later.
Guanabenz reduces the risk of losing walking ability
Safety monitoring recorded 63 serious adverse events among 25 of the 33 children. Investigators judged that 30 of these events were likely or very likely linked to guanabenz. Among them, hallucinations accounted for 24 suspected unexpected serious adverse reactions affecting 18 children. These episodes mainly occurred during the first four months of treatment and generally resolved within months. Four cases involved severe constipation, and one involved temporary low blood pressure with sedation. All four events required brief hospitalization and eventually resolved.
Participants started on oral guanabenz at a dose of 0.15 milligrams per kilogram of body weight daily. Researchers gradually increased doses over approximately six weeks toward each child’s maximum tolerated level, aiming for an optimal dose of 2 milligrams per kilogram per day. After the initial four to six months, investigators observed that children tolerated the medication well. No participants withdrew due to side effects, and the study recorded no life-threatening incidents or fatalities among children receiving guanabenz.
Extended follow-up continues after the clinical trial
The researchers noted that the trial did not randomly assign children to treatment or control groups. Instead, they compared treated participants with historical cases from the Vanishing White Matter Registry. This design means there was no concurrent untreated control group. The team emphasized that a long-term extension study is necessary to confirm the potential disease-modifying effects. It is important to note that guanabenz does not cure VWM. The disease results from genetic defects affecting eukaryotic initiation factor 2B, which controls the cellular integrated stress response targeted by the medication.
Currently, guanabenz lacks regulatory approval for VWM treatment. According to Amsterdam UMC, patients can access the drug for VWM only within research settings at present. A follow-up study is ongoing to monitor long-term effects and to assess different doses of guanabenz in children from the original trial. This research will evaluate walking ability, neurological function, brain imaging, safety, and other clinical outcomes. These new findings represent the first clinical evidence that guanabenz can influence measurable disease progression in children with early-onset VWM, with longer-term research still underway.