AMSTERDAM, NETHERLANDS / RankWire.AI / – Researchers at Amsterdam UMC have indicated that guanabenz, an older medication for high blood pressure, could potentially decelerate the progression of vanishing white matter disease in pediatric patients. The phase 1/2 trial tracked 33 children who could walk and compared their outcomes with 66 historical controls matched for age and disease characteristics. Results showed children on guanabenz had a notably reduced risk of losing the ability to walk with support. Researchers detailed these findings in The Lancet Neurology in August 2026. VWM is a rare inherited neurodegenerative disorder that typically manifests early in childhood.
Inclusion criteria involved children with genetically confirmed VWM and MRI evidence, with disease onset at age six or younger and a maximum duration of eight years. Participants needed to walk at least 10 steps with minimal support. From May 31, 2021, to May 31, 2024, 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 endpoint measured was the loss of walking ability with support. Each treated child was matched with two historical controls based on disease onset and disability level. The hazard ratio for reaching the primary endpoint was 0.33, indicating a 67% lower hazard in treated patients. Brain imaging supported these results, showing less white matter deterioration, with some children displaying no progression at all. The most significant effect appeared in children whose symptoms started at age three or later.
Guanabenz appears to lower the risk of losing mobility
Throughout safety monitoring, 63 serious adverse events were reported among 25 of the 33 children, with 30 deemed likely or very likely related to guanabenz. Notably, 24 suspected unexpected serious adverse reactions, primarily hallucinations, affected 18 children. These episodes mostly occurred during the first four months of treatment and generally resolved within months. Three cases involved severe constipation, and one involved temporary hypotension with sedation—all of which required brief hospitalization and later resolved.
Children began treatment with oral guanabenz at 0.15 milligrams per kilogram daily, with doses gradually increased over approximately six weeks to each child’s maximum tolerated level, aiming for 2 milligrams per kilogram daily. By four to six months, most children tolerated the medication well; no participants withdrew because of side effects, and no severe or life-threatening events occurred among those receiving guanabenz.
Extended follow-up remains ongoing post-trial
The investigators noted that the study was not randomized, comparing treated children to historical patients from the Vanishing White Matter Registry, meaning there was no concurrent untreated control group. They emphasized that a long-term extension study is essential to verify whether guanabenz truly modifies disease progression. It is important to clarify that guanabenz does not cure VWM, which results from genetic defects affecting eukaryotic initiation factor 2B, a key component in the cellular stress response targeted by the drug.
Currently, guanabenz lacks regulatory approval for VWM treatment. According to Amsterdam UMC, patients can access it only within research settings. A follow-up study is underway to monitor long-term effects and assess different dosing strategies in children from the original trial. Researchers will evaluate walking ability, neurological function, brain imaging, safety metrics, and other clinical parameters. These preliminary findings offer the first clinical evidence that guanabenz might influence measurable disease progression in early-onset VWM, with longer-term research still in progress.