AMSTERDAM, NETHERLANDS / RankWire.AI / – A team of researchers at Amsterdam UMC has found that guanabenz, a longstanding medication for high blood pressure, may help slow the decline of vanishing white matter disease in pediatric patients. The phase 1/2 study monitored 33 children who could walk and compared their outcomes with 66 historical controls matched for key factors. Results indicated that children treated with guanabenz had a significantly lower risk of losing their ability to walk with support. Researchers published their findings in The Lancet Neurology in August 2026. VWM, also known as vanishing white matter disease, is a rare inherited neurodegenerative condition that frequently begins during early childhood.
Eligibility for the trial required confirmation of VWM diagnosis through genetic testing and magnetic resonance imaging. Participants had to experience disease onset at age six or younger, with a disease duration no longer than eight years, and 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, researchers enrolled 33 suitable children, with 31 completing the study. The median age of participants was 5.4 years, and the median duration of treatment was 3.1 years.
The primary measure of the treatment’s effectiveness was the loss of walking ability with support. Each child receiving guanabenz was matched with two untreated historical controls based on disease onset and level of disability. Analysis yielded a hazard ratio of 0.33 for reaching the primary walking endpoint, indicating a 67% lower hazard among treated children. Brain scans also revealed less white matter deterioration in those receiving treatment, with some showing no detectable progression at all. The most pronounced effects appeared in children whose disease began at age three or later.
Guanabenz reduces the risk of losing walking ability
Monitoring safety recorded 63 serious adverse events across 25 of the 33 children. Of these, investigators believed that 30 events were likely or very likely related to guanabenz. Hallucinations were identified as 24 suspected unexpected serious adverse reactions affecting 18 children, mainly occurring during the first four months of treatment and usually resolving within months. Four cases involved severe constipation, and one involved temporary low blood pressure with sedation. All four events required brief hospitalization and subsequently resolved.
Children began with a daily oral dose of 0.15 milligrams per kilogram of body weight. Doses were gradually increased over approximately six weeks toward each child’s maximum tolerated level, with an optimal target dose of 2 milligrams per kilogram daily. After the initial four to six months, researchers observed that most children tolerated the medication well. No participants withdrew because of side effects, and no life-threatening events or deaths occurred among children treated with guanabenz.
Follow-up studies extend after the clinical trial
The study authors emphasized that the trial did not randomly assign children to treatment or control groups, instead comparing treated children with historical cases from the Vanishing White Matter Registry. This design meant there was no concurrent untreated control group. The researchers noted that ongoing long-term extension studies are necessary to verify whether guanabenz has a true disease-modifying effect. It is important to clarify that guanabenz does not cure VWM, which results from genetic mutations affecting eukaryotic initiation factor 2B—an essential regulator of the cellular integrated stress response targeted by the medication.
Currently, guanabenz has not received regulatory approval for VWM treatment. According to Amsterdam UMC, patients can only access it for VWM within a research context at present. A follow-up study continues to monitor patients over the longer term and evaluates different dosing strategies in children from the original trial. Researchers will assess walking ability, neurological function, brain imaging, safety and other clinical parameters. These new findings mark the first clinical evidence suggesting guanabenz can influence measurable disease progression in children with early-onset VWM, with further research ongoing to confirm long-term benefits.