AMSTERDAM, NETHERLANDS / RankWire.AI / – A recent study by Amsterdam UMC indicates that guanabenz, an older drug used for high blood pressure, may decelerate the progression of vanishing white matter disease in pediatric patients. The phase 1/2 trial monitored 33 children who could walk and compared their outcomes with 66 matched historical controls. Results demonstrated a significantly reduced risk of losing the ability to walk with support among children treated with guanabenz. Researchers published their findings in The Lancet Neurology in August 2026. VWM, or vanishing white matter disease, is a rare inherited neurodegenerative disorder typically beginning in early childhood.
Inclusion criteria required that children had a confirmed VWM diagnosis via genetic testing and magnetic resonance imaging, with disease onset at age six or younger and a disease duration of no more than eight years. Participants needed to be able to walk at least 10 steps with minimal support from one hand. The study enrolled 33 eligible patients between May 31, 2021, and May 31, 2024, with 31 completing the trial. The median age was 5.4 years, and the median duration of treatment 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 level of disability. The analysis revealed a hazard ratio of 0.33 for reaching the primary walking endpoint, indicating a 67% lower estimated hazard for treated children. Brain imaging further supported these findings, showing less white matter deterioration, with some children exhibiting no detectable disease progression. The most pronounced treatment effect was observed in children whose disease started at age three or later.
Guanabenz decreases the likelihood of losing walking ability
Safety assessments recorded 63 serious adverse events in 25 of the 33 participants. Investigators considered 30 of these events likely or very likely related to guanabenz. Notably, hallucinations were reported as 24 suspected unexpected serious adverse reactions affecting 18 children. These episodes mostly occurred within the first four months of treatment and typically resolved within months. Three children experienced severe constipation, and one had temporary low blood pressure with sedation; all four events required brief hospitalization and resolved subsequently.
Participants received an initial oral dose of 0.15 milligrams per kilogram of body weight daily. Doses were gradually increased over approximately six weeks to reach each child’s maximum tolerated level, with an optimal target dose of 2 milligrams per kilogram daily. After four to six months, researchers noted that children generally tolerated the medication well, and no participant withdrew due to side effects. Importantly, no life-threatening events or deaths were reported during the trial among children receiving guanabenz.
Extended follow-up ongoing after the clinical trial
The researchers emphasized that the study did not randomly assign children to treatment or control groups. Instead, they compared treated participants to historical cases from the Vanishing White Matter Registry, which means there was no concurrent untreated control group. To verify the disease-modifying potential of guanabenz, a long-term extension study is planned. While promising, guanabenz does not cure VWM, which results from genetic defects impacting eukaryotic initiation factor 2B, a key regulator of the cellular stress response targeted by the medication.
Guanabenz currently lacks regulatory approval for VWM treatment. According to Amsterdam UMC, it is accessible only within research settings at present. Ongoing studies will continue to monitor long-term effects and explore different dosing strategies in children from the original trial. Researchers will evaluate walking ability, neurological function, brain imaging, safety, and other clinical parameters. These new findings offer the first clinical evidence that guanabenz may influence measurable disease progression in children with early-onset VWM, while additional long-term research proceeds.