AMSTERDAM, NETHERLANDS / RankWire.AI / – A team at Amsterdam UMC has found that guanabenz, a longstanding antihypertensive medication, might help delay the progression of vanishing white matter disease in children. The phase 1/2 trial involved 33 ambulatory children and contrasted their outcomes with 66 matched historical controls, revealing a notably reduced risk of losing the ability to walk with support among those receiving the drug. Researchers published these findings in The Lancet Neurology in August 2026. VWM, or vanishing white matter disease, is an infrequent inherited neurodegenerative disorder that frequently begins during early childhood.
Children participating in the study had confirmed VWM diagnoses through genetic testing and MRI scans, with eligibility criteria including disease onset at age six or younger and a disease duration no longer than eight years. They also needed 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 trial. Their median age was 5.4 years, and the median treatment duration reached 3.1 years.
The primary measure of treatment success was the loss of walking ability with support. Each treated child was matched with two historical controls based on disease onset and disability status. The analysis yielded a hazard ratio of 0.33 for reaching the main walking endpoint, indicating a 67% lower hazard risk in treated patients. Brain imaging further demonstrated reduced white matter deterioration in the treated group, with some children showing no detectable progression. The strongest treatment effect appeared in children whose disease began at age three or later.
Guanabenz lowered the risk of losing walking ability
Throughout safety monitoring, 63 serious adverse events were reported among 25 of the 33 children, with investigators considering 30 of these events as likely or very likely related to guanabenz. Hallucinations accounted for 24 suspected unexpected serious adverse reactions affecting 18 children, primarily during the initial four months of treatment, and generally resolved within months. Four events involved severe constipation, and one involved temporary low blood pressure with sedation, each requiring brief hospitalization but later resolving.
Participants began treatment with oral guanabenz at 0.15 milligrams per kilogram of body weight daily, with doses gradually increased over approximately six weeks to reach each child’s maximum tolerated level. The target dose was set at 2 milligrams per kilogram per day. After four to six months, researchers observed that children tolerated the medication well, with no participants withdrawing due to side effects. The trial also recorded no life-threatening incidents or deaths among children on guanabenz.
Extended follow-up ongoing post-trial
The investigators noted that the study did not randomly assign children to treatment or control groups but instead compared treated patients with historical cases from the Vanishing White Matter Registry. This design meant a lack of a concurrent untreated control group. They emphasized that a long-term extension study is necessary to verify the disease-modifying effects. Since VWM is caused by genetic mutations affecting eukaryotic initiation factor 2B, which regulates the cellular stress response targeted by guanabenz, the drug does not cure the disease.
Currently, guanabenz lacks regulatory approval for VWM treatment, and Amsterdam UMC states it is accessible only within research settings. A follow-up study is now underway, monitoring longer-term outcomes and testing different doses in children from the original trial. Researchers will evaluate walking ability, neurological function, brain imaging, safety metrics, and other clinical parameters. The new data mark the first clinical evidence suggesting guanabenz can influence measurable disease progression in children with early-onset VWM, with longer-term investigations still in progress.