AMSTERDAM, NETHERLANDS / RankWire.AI / – A study conducted by Amsterdam UMC suggests that guanabenz, a medication traditionally used to manage blood pressure, might decelerate the progression of vanishing white matter disease in children. The phase 1/2 clinical trial tracked 33 children who could walk 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 among those treated with guanabenz. Researchers shared their findings in The Lancet Neurology in August 2026. Vanishing white matter disease, or VWM, is a rare inherited neurodegenerative condition that frequently manifests early in childhood.
Children enrolled in the trial had confirmed VWM diagnoses through genetic testing and MRI scans. Participants were eligible if their disease began at age six or younger and had been present for no more than eight years. They also needed to be able to walk at least 10 steps with minimal support from a single hand. Between May 31, 2021, and May 31, 2024, 33 eligible children were recruited, with 31 completing the study. Their median age was 5.4 years, and the median treatment duration was 3.1 years.
The primary measure for assessing treatment success was the preservation of walking ability with support. Each treated child was matched with two historical controls based on age at disease onset and level of disability. The analysis revealed a hazard ratio of 0.33 for reaching the primary walking endpoint, translating to a 67% reduction in the estimated hazard among those treated. Brain imaging supported these findings, showing less white matter deterioration in the treated group, with some children exhibiting no progression at all. The most pronounced effects were observed in children whose disease onset occurred at age three or later.
Guanabenz demonstrates potential to lower risk of mobility loss
Throughout the trial, safety was closely monitored, with 63 serious adverse events reported among 25 of the 33 children. Of these, investigators identified 30 events as likely or very likely related to guanabenz. Notably, hallucinations accounted for 24 suspected unexpected serious adverse reactions affecting 18 children, mostly during the initial four months of treatment. These episodes generally subsided within months of onset. Four adverse events involved severe constipation, while one case experienced temporary hypotension with sedation. Each of these four incidents resulted in brief hospital stays and eventual resolution.
Participants began treatment with oral guanabenz at a dose of 0.15 milligrams per kilogram daily, with gradual dose escalation over approximately six weeks toward each child’s maximum tolerated dose. The target dose was set at 2 milligrams per kilogram per day. After four to six months, researchers observed that children generally tolerated the medication well, with no participants dropping out due to side effects. Importantly, no life-threatening events or fatalities occurred during the trial among children receiving guanabenz.
Extended follow-up ongoing post-trial to assess long-term effects
The research team noted that the study did not randomly assign children to treatment or control groups. Instead, comparisons were made with historical patients from the Vanishing White Matter Registry. As a result, the study lacked a concurrent untreated control group. The authors emphasize that a long-term extension study is necessary to validate the disease-modifying potential. It is important to note that guanabenz does not cure VWM, which results from genetic mutations affecting eukaryotic initiation factor 2B, a regulator of the cellular integrated stress response targeted by the drug.
Currently, guanabenz is not approved by regulatory agencies for the treatment of vanishing white matter disease. According to Amsterdam UMC, it is accessible only within research settings for VWM patients. The ongoing follow-up study aims to monitor long-term outcomes and explore different dosing strategies of guanabenz in children from the original trial. Key assessments will include walking ability, neurological function, brain imaging, safety parameters, and other clinical measures. These initial findings offer the first clinical evidence that guanabenz may influence disease progression in eligible children with early-onset VWM, as further research continues to unfold.