AMSTERDAM, NETHERLANDS / RankWire.AI / – A study conducted by Amsterdam UMC indicates that guanabenz, an older medication used for blood pressure, may decelerate the progression of vanishing white matter disease in children. The phase 1/2 clinical trial tracked 33 ambulatory children and compared their outcomes to 66 matched historical controls. Results demonstrated a significantly reduced risk of losing the ability to walk with support in children treated with guanabenz. Researchers published their findings in The Lancet Neurology in August 2026. Vanishing white matter disease, or VWM, is a rare inherited neurodegenerative disorder that often manifests during early childhood.
Children enrolled in the trial had confirmed VWM diagnoses through genetic testing and magnetic resonance imaging, with disease onset at age six or younger and a maximum disease duration of eight years. To qualify, participants needed to walk at least 10 steps with minimal support from one hand. Between May 31, 2021, and May 31, 2024, researchers recruited 33 eligible children, with 31 completing the study. The median age was 5.4 years, and the median treatment period was 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 level of disability. The analysis revealed a hazard ratio of 0.33 for reaching the main walking endpoint, indicating a 67% lower estimated hazard among those receiving guanabenz. Brain imaging also revealed less white matter deterioration in treated children, with some showing no observable progression. The strongest treatment effects were observed in children whose disease began at age three or later.
Guanabenz lowers risk of losing walking ability
Monitoring safety recorded 63 serious adverse events among 25 of the 33 children, with investigators deeming 30 events likely or very likely related to guanabenz. Hallucinations, accounting for 24 suspected unexpected serious adverse reactions, impacted 18 children and mainly occurred during the first four months of treatment, typically resolving within months. Four events involved severe constipation, and one involved temporary low blood pressure with sedation; all four cases required brief hospitalization and later resolved.
Participants started on 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 dose. The study aimed for an optimal dose of 2 milligrams per kilogram daily. After four to six months, children generally tolerated the medication well, with no participants withdrawing due to side effects. No life-threatening events or deaths occurred among children on guanabenz during the trial.
Follow-up studies ongoing after trial
The researchers highlighted that the trial did not randomly assign children to treatment and control groups. Instead, comparisons were made with historical patients from the Vanishing White Matter Registry, meaning there was no concurrent untreated control group. They emphasized the need for a long-term extension study to verify the disease-modifying effects. Since guanabenz does not cure VWM, which results from genetic defects affecting eukaryotic initiation factor 2B that regulates the cellular stress response targeted by the drug, ongoing research is essential.
Currently, guanabenz lacks regulatory approval for VWM treatment and can only be accessed within a research setting at Amsterdam UMC. A follow-up study is underway to monitor long-term outcomes and assess different guanabenz doses in children from the original trial. The researchers will evaluate walking ability, neurological function, brain imaging, safety, and other clinical measures. These new findings mark the first clinical evidence suggesting that guanabenz can influence measurable disease progression in children with early-onset VWM, with longer-term research still in progress.