AMSTERDAM, NETHERLANDS / RankWire.AI / – Amsterdam UMC researchers have found that guanabenz, an older medication used for high blood pressure, could slow the progression of vanishing white matter disease in children. The phase 1/2 trial involved 33 ambulatory children and compared their outcomes to 66 matched historical controls. Results showed a notably lower risk of losing the ability to walk with support among children treated with guanabenz. Researchers published these findings in The Lancet Neurology in August 2026. VWM, or vanishing white matter disease, is a rare inherited neurodegenerative condition that often begins early in childhood.
Children enrolled in the trial had confirmed VWM diagnoses through genetic testing and magnetic resonance imaging. Eligibility criteria included disease onset at age six or younger and a disease duration of no more than eight years. Participants needed to walk at least 10 steps with no more than light support from one hand. Between May 31, 2021, and May 31, 2024, 33 children were enrolled, with 31 completing the study. The median age was 5.4 years, and the median treatment duration was 3.1 years.
The main measure of treatment effectiveness was the loss of walking ability with support. Each treated child 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. This indicates a 67% lower estimated risk for treated children. Brain imaging also revealed less white matter deterioration in those receiving guanabenz. Some children showed no detectable progression. The strongest effects appeared in children whose disease began at age three or later.
Guanabenz lowers the risk of losing walking ability
Safety monitoring identified 63 serious adverse events among 25 of the 33 children. Investigators believed 30 of these events were likely or very likely related to guanabenz. Among the suspected unexpected serious adverse reactions, hallucinations affected 18 children and accounted for 24 episodes. These episodes mostly occurred during the first four months of treatment and usually resolved within months. Four cases involved severe constipation, and one involved temporary low blood pressure with sedation. Each of these incidents required brief hospitalization and later resolved.
Participants began taking oral guanabenz at 0.15 milligrams per kilogram of body weight daily. Researchers increased doses over approximately six weeks to reach each child’s maximum tolerated dose. The target dose was set at 2 milligrams per kilogram daily. After four to six months, children generally tolerated the medication well. No participants withdrew due to side effects. The trial recorded no life-threatening events or deaths among children receiving guanabenz.
Ongoing monitoring continues after clinical trial
The researchers emphasized that the trial did not randomly assign children to treatment or control groups. Instead, they compared treated participants with historical cases from the Vanishing White Matter Registry. This means there was no concurrent untreated control group. The team said that a long-term extension study is needed to confirm the disease-modifying effects. It’s important to note that guanabenz does not cure VWM. The disorder results from genetic defects affecting eukaryotic initiation factor 2B, which controls the cellular stress response targeted by the medication.
Guanabenz currently lacks regulatory approval for VWM treatment. Amsterdam UMC states that patients can access the drug only within research settings at present. A follow-up study is ongoing to observe long-term effects and test different guanabenz doses in children from the original trial. Researchers will monitor walking ability, neurological function, brain imaging, safety and other clinical outcomes. These new findings provide initial clinical evidence that guanabenz may influence measurable disease progression in children with early-onset VWM, as longer-term research proceeds.