AMSTERDAM, NETHERLANDS / RankWire.AI / – A team of researchers at Amsterdam UMC has indicated that guanabenz, an established antihypertensive medication, might slow the progression of vanishing white matter disease in pediatric patients. Their phase 1/2 clinical trial involved 33 ambulatory children and included a comparison with 66 historical controls matched for relevant factors. The findings revealed a significantly reduced risk of losing the ability to walk with support among children treated with guanabenz. The study results were published in The Lancet Neurology in August 2026 by researchers. Vanishing white matter disease, or VWM, is a rare inherited neurodegenerative condition that typically manifests during early childhood.
Children included in the trial had their VWM diagnosis confirmed via genetic testing and magnetic resonance imaging. To qualify, patients needed disease onset at age six or younger and a disease duration of no more than eight years. Participants were required to walk at least 10 steps with no more than light support from one hand. Between May 31, 2021, and 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 measure of treatment success was the loss of walking ability with support. Each treated child was matched with two untreated 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. Notably, the strongest treatment effect was observed among children whose disease began at age three or later.
Guanabenz Demonstrates Potential to Reduce Risk of Mobility Loss
During safety assessments, 63 serious adverse events were documented among 25 of the 33 children. Investigators determined that 30 of these events were likely or very likely related to guanabenz. Among these, hallucinations were identified as 24 suspected unexpected serious adverse reactions affecting 18 children. These episodes mainly occurred during the first four months of treatment and generally resolved within months. Four events involved severe constipation, and one case involved temporary hypotension with sedation; all of these episodes required brief hospital stays but later resolved.
Children started on oral guanabenz at a dose of 0.15 milligrams per kilogram of body weight daily, with doses gradually increased over about six weeks toward each child’s maximum tolerated level. The target dose was set at 2 milligrams per kilogram daily. After four to six months, researchers observed that most children tolerated the medication well, with no participants dropping out due to side effects. Importantly, no life-threatening events or deaths were reported among those receiving guanabenz.
Extended Monitoring Continues Following the Clinical Trial
The researchers emphasized that the study did not employ random assignment for treatment and control groups. Instead, they compared treated children with historical patients from the Vanishing White Matter Registry. This approach means there was no concurrent untreated control group, and the findings require confirmation through a long-term extension study to verify the disease-modifying potential. It is important to note that guanabenz is not a cure for VWM, which results from genetic mutations affecting eukaryotic initiation factor 2B, a key regulator of the cellular stress response targeted by the drug.
Currently, guanabenz lacks regulatory approval for the treatment of vanishing white matter disease. According to Amsterdam UMC, the medication can only be accessed within research settings at this time. A follow-up study is underway to monitor long-term effects and assess different dosage levels in children from the original trial. Researchers will examine metrics such as walking ability, neurological function, brain imaging, safety concerns, and other clinical indicators. These new findings represent the first clinical evidence suggesting that guanabenz may influence measurable aspects of disease progression in children with early-onset VWM, with further long-term research still in progress.