AMSTERDAM, NETHERLANDS / RankWire.AI / – In Amsterdam, during August 2026, Amsterdam UMC disclosed that guanabenz, an older antihypertensive medication, might help decelerate the decline caused by vanishing white matter disease in young patients. The initial phase 1/2 trial tracked 33 children who could walk independently and compared their outcomes with 66 historical controls matched for relevant factors. Results indicated a notably reduced risk of losing the ability to walk with support in children receiving guanabenz. The study’s findings appeared in The Lancet Neurology in August 2026. Vanishing white matter disease, or VWM, is a rare inherited neurodegenerative condition that typically manifests early in childhood.
Participants in the trial had confirmed VWM diagnoses via genetic testing and MRI scans. Eligibility criteria mandated disease onset at age six or younger and a disease duration of no more than eight years. Children also needed to be able to walk at least 10 steps with minimal support from one hand. Between May 31, 2021, and May 31, 2024, researchers enrolled 33 suitable patients, with 31 completing the study. The median age was 5.4 years, and the median treatment duration reached 3.1 years.
The primary measure of treatment success was the prevention of walking loss with support. Each treated child was matched with two historical controls based on disease onset and disability level. The analysis yielded a hazard ratio of 0.33 for reaching the primary walking endpoint, indicating a 67% lower estimated hazard among those treated. Brain imaging supported these findings, showing less white matter deterioration, with some children displaying no detectable progression. The strongest treatment effects were observed in children whose disease began at age three or later.
Guanabenz lowered the risk of losing walking ability
Monitoring safety revealed 63 serious adverse events among 25 of the 33 children, with investigators considering 30 of these events as probably or definitely related to guanabenz. Hallucinations accounted for 24 suspected unexpected serious adverse reactions affecting 18 children, mainly during the first four months of treatment, and most episodes resolved within months of onset. Three instances involved severe constipation, and one case involved temporary low blood pressure with sedation, each requiring brief hospitalization and later recovery.
Children started on oral guanabenz at a dose of 0.15 milligrams per kilogram of body weight daily. Doses were gradually increased over approximately six weeks to reach each child’s maximum tolerated dose, with an optimal target of 2 milligrams per kilogram daily. After four to six months, investigators observed that children generally tolerated the medication well. No participants withdrew due to side effects, and there were no reports of life-threatening events or fatalities among children on guanabenz.
Extended follow-up efforts are ongoing beyond the initial trial
The researchers emphasized that the study’s design did not involve random assignment of children to treatment or control groups. Instead, they compared treated children to historical cases from the Vanishing White Matter Registry. This means there was no concurrent untreated control group. The team noted that a longer-term extension study is necessary to verify the potential disease-modifying effects. It is important to clarify that guanabenz does not cure VWM, which results from genetic mutations affecting eukaryotic initiation factor 2B, a regulator of the cellular integrated stress response that the drug targets.
Currently, guanabenz lacks formal regulatory approval for VWM treatment. According to Amsterdam UMC, patients may only access the drug within research settings at this time. A follow-up investigation is ongoing, focusing on longer-term monitoring and testing different guanabenz doses in children from the original trial. Researchers aim to assess walking ability, neurological function, brain imaging, safety, and other clinical parameters. These preliminary results mark the first clinical evidence suggesting guanabenz can influence measurable disease progression in children with early-onset VWM, while extended research continues to unfold.