AMSTERDAM, NETHERLANDS / RankWire.AI / – A team of researchers at Amsterdam UMC has reported that guanabenz, an older medication used for managing blood pressure, might decelerate the progression of vanishing white matter disease in pediatric patients. Their phase 1/2 clinical trial involved tracking 33 children who could walk independently and comparing their outcomes to 66 historical controls matched for key factors. The findings indicated a significantly decreased risk of losing the ability to walk with support among children treated with guanabenz. The study’s results were published by Researchers in The Lancet Neurology in August 2026. Vanishing white matter disease, or VWM, is a rare inherited neurodegenerative disorder that usually manifests early in childhood.
Participants in the trial were children with a confirmed VWM diagnosis through genetic testing and magnetic resonance imaging, with criteria requiring disease onset at age six or younger and a disease duration not exceeding eight years. These children had to be able to walk at least ten steps with support limited to light assistance from one hand. Between May 31, 2021, and May 31, 2024, a total of 33 eligible children were enrolled, with 31 completing the study. Their median age was 5.4 years, and the median duration of treatment was 3.1 years.
The primary measure of treatment efficacy was the loss of walking ability with support. Each child receiving guanabenz was matched with two historical controls based on disease onset and level of disability. The analysis revealed a hazard ratio of 0.33 for reaching the primary endpoint of losing walking capacity, indicating a 67% reduction in the hazard among treated patients. Brain imaging supported these findings, showing less white matter deterioration in children who received the medication, with some displaying no detectable progression at all. The most notable treatment effects were observed in children whose disease began at age three or later.
Guanabenz decreases the likelihood of losing walking ability
Monitoring safety, the study recorded 63 serious adverse events across 25 of the 33 children, with investigators determining that 30 of these events were likely or very likely related to guanabenz. Notably, hallucinations accounted for 24 suspected unexpected serious adverse reactions affecting 18 children, primarily occurring during the first four months of treatment and generally resolving within months. Among these adverse events, three involved severe constipation, and one was a temporary episode of low blood pressure with sedation. All four cases required brief hospitalization but eventually resolved without long-term issues.
Participants began treatment with an oral dose of 0.15 milligrams per kilogram of body weight daily, which was gradually increased over roughly six weeks to reach each child’s maximum tolerated dose. The study identified 2 milligrams per kilogram daily as the optimal target dose. After four to six months, researchers observed that children generally tolerated the treatment well, with no participants withdrawing due to side effects, and no life-threatening events or deaths occurring among those receiving guanabenz.
Extended follow-up remains ongoing beyond the initial trial phase
The investigators emphasized that the trial did not involve random assignment of children to treatment or control groups. Instead, treated participants were compared to historical cases from the Vanishing White Matter Registry, meaning the study lacked a concurrent untreated control group. They suggested that a long-term extension study is necessary to confirm whether guanabenz can indeed modify disease progression. It is important to note that guanabenz is not a cure for VWM, as the disorder results from genetic defects impacting eukaryotic initiation factor 2B, which controls the cellular integrated stress response targeted by the medication.
Currently, guanabenz has not received regulatory approval for VWM treatment, and Amsterdam UMC states that the medication is accessible only within research settings for patients with VWM. Ongoing long-term monitoring and further studies are examining different dosing regimens of guanabenz in children from the original trial, tracking parameters such as walking ability, neurological function, brain imaging, safety, and other clinical markers. These recent findings mark the first clinical evidence suggesting that guanabenz might influence measurable disease progression in children with early-onset VWM, while extended research continues to verify its long-term effects.