AMSTERDAM, NETHERLANDS / RankWire.AI / – Researchers at Amsterdam UMC have reported that guanabenz, an established medication for high blood pressure, could potentially slow the progression of vanishing white matter disease in children. The study, conducted as a phase 1/2 trial, involved 33 ambulatory pediatric patients and compared their outcomes with 66 matched historical controls. The findings indicated a significantly decreased risk of losing the ability to walk with support among those receiving guanabenz. Researchers shared these results in The Lancet Neurology in August 2026. Vanishing white matter disease, or VWM, is a rare inherited neurodegenerative disorder that typically manifests early in childhood.
The trial selected children whose VWM diagnosis was confirmed through genetic testing and magnetic resonance imaging. To qualify, participants needed to have experienced disease onset at age six or younger and have a disease duration of no more than eight years. Additionally, children had 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, 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 of treatment success focused on loss 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 main walking endpoint, translating to a 67% lower estimated hazard among treated participants. Brain imaging supported these findings, showing less white matter deterioration in children receiving guanabenz, with some displaying no detectable disease progression. The strongest treatment effect was observed in children whose disease began at age three or older.
Guanabenz Lessens Risk of Losing Walking Ability
During safety assessments, 63 serious adverse events were documented across 25 of the 33 children. Investigators judged 30 of these events as likely or very likely related to guanabenz. Hallucinations were a concern, with 24 suspected unexpected serious adverse reactions affecting 18 children. These episodes mostly occurred within the first four months of treatment and generally resolved within months of onset. Three cases involved severe constipation, while one case involved temporary low blood pressure with sedation. Each of these four incidents required brief hospitalization and later resolved.
Children began treatment with oral guanabenz at 0.15 milligrams per kilogram of body weight daily. Doses were gradually increased over roughly six weeks toward each child’s maximum tolerated level, with an optimal target dose set at 2 milligrams per kilogram daily. After four to six months, investigators observed that children generally tolerated the medication well. No participants withdrew due to side effects, and no life-threatening events or fatalities occurred among those on guanabenz.
Extended Follow-Up Underway Post-Study
The researchers emphasized that the trial was not randomized; instead, treated children were compared to historical cases from the Vanishing White Matter Registry. This approach resulted in the absence of a concurrent untreated control group. They noted that ongoing long-term extension studies are necessary to confirm whether guanabenz has a true disease-modifying effect. It is important to clarify that guanabenz does not cure VWM. The condition arises from genetic mutations affecting eukaryotic initiation factor 2B, a key regulator of the cellular integrated stress response targeted by the drug.
Currently, guanabenz is not approved by regulatory agencies for treating VWM. According to Amsterdam UMC, it is accessible only within research settings for this condition. A follow-up study is now in progress, focusing on longer-term observation and testing different doses of guanabenz in children from the original trial. The researchers plan to monitor walking ability, neurological function, brain imaging, safety parameters, and other clinical markers. These initial findings provide the first clinical evidence that guanabenz may influence measurable disease progression in children with early-onset VWM, while longer-term investigations continue.