AMSTERDAM, NETHERLANDS / RankWire.AI / – Researchers at Amsterdam UMC report that guanabenz, an older blood pressure drug, may slow vanishing white matter disease in children. The phase 1/2 trial followed 33 ambulatory children and compared their outcomes with 66 matched historical controls. The study found a significantly lower risk of losing the ability to walk with support among children receiving guanabenz. Researchers published the results in The Lancet Neurology in August 2026. Vanishing white matter disease, or VWM, is a rare inherited neurodegenerative disorder that often begins in early childhood.
The trial included children whose VWM diagnosis had confirmation through genetic testing and magnetic resonance imaging. Eligibility required disease onset at age six or younger and a disease duration of no more than eight years. Children also had to walk at least 10 steps with no more than light support from one hand. Researchers enrolled 33 eligible patients between May 31, 2021, and May 31, 2024. Thirty-one completed the trial. Their median age was 5.4 years, while the median treatment period reached 3.1 years.
Researchers used loss of walking with support as the primary measure of treatment effectiveness. They matched each treated child with two untreated historical controls based on disease onset and disability. The analysis produced a hazard ratio of 0.33 for reaching the main walking endpoint. That corresponds to a 67% lower estimated hazard among treated patients. Brain scans also showed less white matter deterioration in treated children, with some showing no detectable progression. Researchers reported the strongest treatment effect among children whose disease began at age three or later.
Guanabenz reduced risk of losing walking ability
Safety monitoring recorded 63 serious adverse events among 25 of the 33 children. Investigators judged 30 events as likely or very likely related to guanabenz. Hallucinations accounted for 24 suspected unexpected serious adverse reactions and affected 18 children. These episodes occurred mainly during the first four months of treatment and generally resolved within months of their first appearance. Three cases involved severe constipation, while one involved temporary low blood pressure with sedation. Each of those four events required a brief hospital stay and later resolved.
Participants started oral guanabenz at 0.15 milligrams per kilogram of body weight each day. Researchers then increased doses over about six weeks toward each child’s maximum tolerated level. The study set an optimal target dose of 2 milligrams per kilogram daily. After the first four to six months, investigators reported that children generally tolerated the treatment well. No participant left the study because of side effects. The trial also recorded no life-threatening events or deaths among children receiving guanabenz.
Long-term follow-up continues after clinical trial
The researchers cautioned that the trial did not randomly assign children to treatment and control groups. Instead, they compared treated participants with historical patients from the Vanishing White Matter Registry. That design means the study lacked a concurrent untreated control group. The researchers said a long-term extension study should confirm the disease-modifying effect. Guanabenz also does not cure VWM. The disease stems from genetic defects affecting eukaryotic initiation factor 2B, which regulates the cellular integrated stress response targeted by the drug.
Guanabenz currently has no regulatory approval for treating vanishing white matter disease. Amsterdam UMC says patients can access it for VWM only within a research setting at present. A follow-up study is continuing longer-term monitoring and examining different guanabenz doses in children from the original trial. Researchers will track walking ability, neurological function, brain imaging, safety and other clinical measures. The new findings provide the first clinical evidence that guanabenz can alter measurable disease progression in eligible children with early-onset VWM, while longer-term research continues.