AMSTERDAM, NETHERLANDS / RankWire.AI / – A team of researchers at Amsterdam UMC has indicated that guanabenz, an older medication used for high blood pressure, could potentially slow down the progression of vanishing white matter disease in pediatric patients. The initial phase 1/2 trial involved 33 children who were able to walk and was compared against 66 historical controls with similar characteristics. The findings revealed a significantly reduced risk of losing the ability to walk with support among children treated with guanabenz. Researchers presented their results in The Lancet Neurology in August 2026. Vanishing white matter disease, or VWM, is a rare inherited neurodegenerative condition that often manifests early in childhood.
Children included in the trial had confirmed VWM diagnoses through genetic testing and magnetic resonance imaging. To qualify, they had to show disease onset at age six or younger and have a disease duration of no more than eight years. Additionally, participants were required to be able to walk at least 10 steps with minimal 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 used to assess treatment efficacy was the loss of walking ability with support. Each treated participant was matched with two historical controls based on disease onset and level of disability. The analysis showed a hazard ratio of 0.33 for reaching the primary walking endpoint, equating to a 67% lower estimated hazard among those receiving guanabenz. Brain imaging also demonstrated less white matter deterioration in treated children, with some showing no detectable disease progression. The most pronounced treatment effect was observed in children whose disease started at age three or older.
Guanabenz appears to decrease the risk of losing the ability to walk
Monitoring safety revealed 63 serious adverse events among 25 of the 33 children. Investigators identified 30 of these events as likely or very likely related to guanabenz. Notably, hallucinations accounted for 24 suspected unexpected serious adverse reactions affecting 18 children, primarily during the first four months of treatment. These episodes generally resolved within months. Four events involved severe constipation, while one case experienced temporary low blood pressure with sedation. All four episodes required brief hospitalization and later resolved.
Children began treatment with oral guanabenz at a starting dose of 0.15 milligrams per kilogram of body weight daily. Dose escalation occurred over approximately six weeks until reaching each child’s maximum tolerated dose. The study targeted an optimal dose of 2 milligrams per kilogram per day. After four to six months, investigators reported that most children tolerated the medication well, with no participants withdrawing due to side effects. There were no reports of life-threatening events or deaths among the children on guanabenz.
Extended follow-up continues beyond the initial clinical trial
The research team emphasized that the trial did not involve random assignment of children to treatment or control groups. Instead, they compared the treated children with historical cases from the Vanishing White Matter Registry. This approach means a concurrent untreated control group was not present. The team advocates for a long-term extension study to verify the potential disease-modifying effects. It is important to note that guanabenz does not cure VWM, which results from genetic mutations impacting eukaryotic initiation factor 2B, a regulator of the cellular stress response targeted by the medication.
Currently, guanabenz lacks regulatory approval for VWM treatment. Amsterdam UMC states that patients can only access it within a research setting. A follow-up study is ongoing, focusing on long-term monitoring and testing different guanabenz doses in children from the original trial. Researchers plan to evaluate walking ability, neurological health, brain imaging, safety, and other clinical outcomes. These new findings represent the first clinical evidence suggesting guanabenz’s capacity to influence measurable disease progression in children with early-onset VWM, while further long-term research is underway.