AMSTERDAM, NETHERLANDS / RankWire.AI / – In the realm of neurodegenerative disorders, vanishing white matter disease (VWM) remains a challenging condition with limited treatment options. Recent research from Amsterdam UMC suggests that guanabenz, an established blood pressure medication, might have a role in delaying the disease’s progression in pediatric patients. The phase 1/2 trial involved 33 children living with VWM and contrasted their results with 66 matched historical controls. The findings revealed a notably reduced risk of children losing the ability to walk with support when treated with guanabenz. The researchers published their results in The Lancet Neurology in August 2026. VWM, an inherited neurodegenerative disorder, typically manifests during early childhood.
The study participants were children diagnosed with VWM confirmed via genetic testing and magnetic resonance imaging. To qualify, children had to experience disease onset at age six or younger and have a disease duration of no more than eight years. Additionally, they needed to be able to walk at least 10 steps with no more than light support from one hand. Between May 31, 2021, and May 31, 2024, a total of 33 eligible children were enrolled, with 31 completing the trial. Their median age was 5.4 years, and the median treatment duration was 3.1 years.
The primary measure for assessing treatment efficacy was the loss of walking ability with support. Each treated child was matched with two historical controls based on disease onset and disability levels. The analysis yielded a hazard ratio of 0.33 for reaching the primary walking endpoint, indicating a 67% lower estimated hazard in the guanabenz group. Brain imaging supported these findings, showing reduced white matter deterioration among treated children, with some exhibiting no detectable progression. The most significant treatment effect was observed in children whose disease onset occurred at age three or later.
Guanabenz lowered the risk of losing walking capacity
Monitoring for safety identified 63 serious adverse events in 25 of the 33 children. Of these, investigators judged 30 events as likely or very likely related to guanabenz. Among these adverse events, hallucinations were the most common, with 24 suspected unexpected serious adverse reactions affecting 18 children. These episodes primarily happened during the first four months of treatment and typically resolved within months of onset. Four cases involved severe constipation, while one case involved temporary hypotension with sedation; all four required brief hospitalization and later resolved.
Participants began treatment with oral guanabenz at a dose of 0.15 milligrams per kilogram of body weight daily. Doses were gradually increased over approximately six weeks to reach each child’s maximum tolerated level. The study targeted an optimal dose of 2 milligrams per kilogram per day. After the initial four to six months, children generally tolerated the medication well, with no participants withdrawing due to side effects. No life-threatening incidents or deaths occurred among children receiving guanabenz during the trial.
Extended follow-up ongoing after clinical trial completion
The researchers emphasized that the trial was not randomized. Instead, they compared treated children with historical patients from the Vanishing White Matter Registry, meaning a concurrent untreated control group was absent. They suggested that a long-term extension study is necessary to verify the potential disease-modifying effects observed. It is important to note that guanabenz does not cure VWM, which results from genetic mutations affecting eukaryotic initiation factor 2B, a key regulator of the cellular stress response targeted by the drug.
At present, guanabenz has not received regulatory approval for treating VWM. According to Amsterdam UMC, the medication can only be accessed for VWM within research settings. A follow-up study is underway to monitor long-term outcomes and assess different dosing strategies in children from the original trial. Researchers will continue to evaluate walking ability, neurological function, brain imaging, safety, and other clinical measures. These initial findings offer the first clinical evidence that guanabenz may influence measurable disease progression in children with early-onset VWM, while ongoing research continues to explore its potential benefits.