AMSTERDAM, NETHERLANDS / RankWire.AI / – Researchers at Amsterdam UMC have reported that the older antihypertensive medication guanabenz might help delay the decline associated with vanishing white matter disease in pediatric patients. The phase 1/2 clinical trial monitored 33 ambulatory children and compared their results with 66 matched historical controls, revealing a notably reduced risk of losing the ability to walk with support in children treated with guanabenz. Researchers shared their findings in The Lancet Neurology in August 2026. Vanishing white matter disease, also known as VWM, is a rare inherited neurodegenerative disorder that typically manifests during early childhood.
The study included children whose diagnosis of VWM was confirmed through genetic testing and magnetic resonance imaging, with eligibility criteria requiring disease onset at age six or younger and a disease duration not exceeding eight years. Participants needed to be able to walk at least ten steps with only light support from one hand. Between May 31, 2021, and May 31, 2024, 33 eligible children were enrolled, with 31 completing the trial. Their median age was 5.4 years, and the median duration of treatment was 3.1 years.
The primary measure of the treatment’s effectiveness was the preservation of walking ability with support. Each treated child was matched with two historical controls based on disease onset and severity. The analysis yielded a hazard ratio of 0.33 for reaching the primary walking endpoint, indicating a 67% lower estimated hazard among those receiving guanabenz. Brain imaging supported these findings, showing less white matter deterioration in treated children, with some exhibiting no detectable progression at all. The strongest treatment effects were observed in children whose disease started at age three or later.
Guanabenz appears to lower the risk of losing walking ability
Throughout the trial, safety monitoring identified 63 serious adverse events among 25 of the 33 children; investigators considered 30 of these events likely or very likely related to guanabenz. Hallucinations were among the 24 suspected unexpected serious adverse reactions, affecting 18 children, predominantly during the first four months of treatment, with symptoms generally resolving within months. Four cases involved severe constipation, and one case involved transient low blood pressure with sedation—all of which required brief hospitalization and eventually resolved.
Participants began treatment with oral guanabenz at a starting dose of 0.15 milligrams per kilogram of body weight daily, which was gradually increased over approximately six weeks to reach each child’s maximum tolerated dose. The study set a target dose of 2 milligrams per kilogram per day. After four to six months, researchers observed that children generally tolerated the medication well, with no participants withdrawing due to side effects, and no life-threatening events or fatalities reported among children receiving guanabenz.
Ongoing long-term monitoring follows the initial trial
The investigators emphasized that the study was not randomized; instead, children receiving guanabenz were compared with historical patients from the Vanishing White Matter Registry, meaning there was no concurrent untreated control group. They suggest that a long-term extension study is necessary to confirm the potential disease-modifying effects observed. It is important to note that guanabenz does not cure VWM, as the disease results from genetic mutations impacting eukaryotic initiation factor 2B, which regulates the cellular integrated stress response targeted by the drug.
Currently, guanabenz has no official regulatory approval for the treatment of vanishing white matter disease. According to Amsterdam UMC, it is available to patients with VWM only within a research context at present. A follow-up study is ongoing, aiming to monitor patients over a longer period and evaluate different doses of guanabenz in children from the initial trial. Researchers will assess walking ability, neurological function, brain imaging, safety, and other clinical parameters. These initial findings represent the first clinical evidence that guanabenz may influence measurable disease progression in children with early-onset VWM, while longer-term research remains in progress.
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