AMSTERDAM, NETHERLANDS / RankWire.AI / – Researchers at Amsterdam UMC have found that guanabenz, an older drug used to treat high blood pressure, could help delay the decline of vanishing white matter disease in children. The phase 1/2 trial involved 33 children who could walk and compared their outcomes to 66 historical controls with similar conditions. Results showed a notably lower risk of losing the ability to walk with support among children taking guanabenz. Researchers published their findings in The Lancet Neurology in August 2026. VWM, or vanishing white matter disease, is a rare inherited neurodegenerative disorder that typically begins early in childhood.
The study included children whose VWM diagnosis was confirmed through genetic testing and MRI scans. To qualify, children had to show disease onset at age six or younger and have a disease duration of no more than eight years. Participants also needed to walk at least 10 steps with no more than light support from one hand. The researchers enrolled 33 eligible children between May 31, 2021, and May 31, 2024. Of these, 31 completed the trial. The median age was 5.4 years, and the median treatment period was 3.1 years.
The main measure of treatment success was the loss of walking ability with support. Each child receiving guanabenz was matched with two historical controls based on disease onset and disability level. The analysis revealed a hazard ratio of 0.33 for reaching the primary walking endpoint. This indicates a 67% lower estimated hazard for treated children. Brain imaging supported these findings, showing less white matter deterioration among treated participants, some of whom exhibited no detectable progression. The strongest effects appeared in children whose disease started at age three or later.
Guanabenz lowers the risk of losing walking ability
Safety was closely monitored. There were 63 serious adverse events reported in 25 of the 33 children. Investigators believed that 30 of these events were likely or very likely related to guanabenz. Among these, hallucinations were the most common, affecting 18 children and accounting for 24 suspected unexpected serious adverse reactions. Most hallucinations occurred during the first four months of treatment and generally resolved within months. Three children experienced severe constipation, and one had temporary low blood pressure with sedation. All four events required brief hospitalization and later resolved.
Initially, children began taking oral guanabenz at 0.15 milligrams per kilogram of body weight daily. The dose was gradually increased over roughly six weeks to 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. No one withdrew due to side effects. The study recorded no life-threatening events or deaths related to guanabenz among the children.
Extended follow-up ongoing beyond initial trial
The scientists warned that the study did not randomly assign children to treatment or control groups. Instead, they compared treated children to past patients from the Vanishing White Matter Registry. This means there was no concurrent untreated control group. The researchers emphasized that a long-term extension study is necessary to confirm whether guanabenz can modify the disease. It’s important to note that guanabenz does not cure VWM. The disease results from genetic mutations affecting eukaryotic initiation factor 2B, which controls the cellular stress response targeted by the drug.
Guanabenz is not currently approved by regulatory agencies for treating vanishing white matter disease. According to Amsterdam UMC, it is only accessible for VWM within research settings at this time. A follow-up study is ongoing to monitor long-term effects and test different doses in children from the initial trial. Researchers will assess walking ability, neurological functions, brain scans, safety, and other clinical outcomes. These new results offer the first clinical evidence that guanabenz may slow measurable disease progression in children with early-onset VWM, with longer-term research still in progress.