AMSTERDAM, NETHERLANDS / RankWire.AI / – Amsterdam UMC researchers have discovered that guanabenz, an older medication used for blood pressure control, may decelerate the progression of vanishing white matter disease in children. The phase 1/2 trial involved 33 ambulatory children and compared their outcomes with 66 matched historical controls. The findings indicated a significantly reduced risk of losing the ability to walk with support among children who received guanabenz. Researchers published their results in The Lancet Neurology in August 2026. Vanishing white matter disease, or VWM, is a rare inherited neurodegenerative disorder that often manifests in early childhood.
The study included children with VWM confirmed through genetic testing and magnetic resonance imaging. Eligibility criteria mandated disease onset at age six or younger and a disease duration no longer than eight years. Additionally, children were required 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, with a median treatment duration of 3.1 years.
The primary indicator of treatment efficacy was loss of walking ability with support. Each treated child was matched with two historical controls based on disease onset and disability severity. The analysis yielded a hazard ratio of 0.33 for reaching the primary walking endpoint, indicating a 67% lower estimated hazard in the guanabenz group. Brain imaging also revealed less white matter deterioration among treated children, some showing no detectable progression. The most pronounced treatment effect was observed in children whose disease began at age three or later.
Guanabenz associated with a decreased risk of losing walking capability
Safety assessments identified 63 serious adverse events among 25 of the 33 children. Of these, investigators considered 30 events as likely or very likely related to guanabenz. Hallucinations were responsible for 24 suspected unexpected serious adverse reactions affecting 18 children. These episodes mainly occurred during the initial four months of treatment and generally resolved within months. Four adverse events involved severe constipation, and one case involved temporary low blood pressure with sedation; each required brief hospitalization and later resolved.
Participants commenced oral guanabenz at 0.15 milligrams per kilogram of body weight daily. Researchers gradually increased the doses over approximately six weeks to reach each child’s maximum tolerated level, with an optimal target dose of 2 milligrams per kilogram daily. After four to six months, children generally tolerated the medication well, with no dropouts due to side effects. The trial recorded no life-threatening incidents or deaths related to guanabenz among participating children.
Extended monitoring ongoing post-clinical trial
The study authors emphasized that the trial lacked random assignment, as children were compared with historical patients from the Vanishing White Matter Registry rather than a concurrent untreated control group. They recommended conducting a long-term extension study to verify the potential disease-modifying effects. It is important to note that guanabenz does not cure VWM, which results from genetic mutations affecting eukaryotic initiation factor 2B, a key regulator of the cellular integrated stress response targeted by the drug.
Currently, guanabenz has not received regulatory approval for VWM treatment. According to Amsterdam UMC, the drug is accessible to patients only within research settings at present. A follow-up study continues to monitor long-term outcomes and investigates various guanabenz dosing regimens in children from the original trial. The research team plans to track walking ability, neurological function, brain imaging, safety, and other clinical parameters. These initial findings offer the first clinical evidence that guanabenz may influence measurable disease progression in children with early-onset VWM, with further long-term investigation underway.