AMSTERDAM, NETHERLANDS / RankWire.AI / – According to Amsterdam UMC, guanabenz, an older medication used to manage blood pressure, shows promise in slowing the progression of vanishing white matter disease in pediatric patients. The phase 1/2 trial observed 33 children who could walk and compared their outcomes to 66 historical controls matched for disease characteristics. Results indicated a significantly decreased risk of losing the ability to walk with support among children treated with guanabenz. The study findings were published in The Lancet Neurology in August 2026 by researchers. Vanishing white matter disease, or VWM, is a rare inherited neurodegenerative condition that often manifests early in childhood.
Participants in the trial were children with confirmed VWM diagnoses through genetic testing and MRI scans. Eligibility criteria included disease onset at age six or younger and a disease duration not exceeding eight years. They also needed to be able to walk at least 10 steps with only minimal support from one hand. Between May 31, 2021, and May 31, 2024, 33 eligible children were enrolled, with 31 completing the study. Their median age was 5.4 years, and the median duration of treatment was 3.1 years.
The primary measure of efficacy was the loss of walking ability with support. Each treated participant was matched with two untreated historical controls based on disease onset and severity. The analysis revealed a hazard ratio of 0.33 for reaching the primary walking endpoint, indicating a 67% lower hazard among those receiving guanabenz. Brain imaging further supported these findings, showing less white matter deterioration, with some children exhibiting no detectable progression. The most notable effects were observed in children whose disease began at age three or later.
Guanabenz shows promise in reducing risk of mobility loss
During safety assessments, 63 serious adverse events were documented among 25 of the 33 children. Investigators considered 30 of these events as likely or very likely related to guanabenz. Among these, hallucinations were the most frequent, with 24 suspected unexpected serious adverse reactions impacting 18 children. These episodes mainly occurred during the initial four months of treatment and generally resolved within months. Four instances involved severe constipation, and one case involved temporary hypotension with sedation; all four required brief hospitalization and subsequently resolved.
Children received an initial daily dose of 0.15 milligrams per kilogram of body weight, with gradual dose escalation over approximately six weeks toward each child’s maximum tolerated dose. The target dose was set at 2 milligrams per kilogram daily. After four to six months, investigators reported that tolerability was generally good, with no participants withdrawing due to side effects. No life-threatening events or deaths occurred among children receiving guanabenz during the trial.
Extended monitoring is ongoing post-clinical trial
The research team emphasized that the trial lacked random assignment, as children were compared to historical controls from the Vanishing White Matter Registry rather than a concurrent untreated group. Therefore, long-term extension studies are necessary to verify the potential disease-modifying effects. It’s important to note that guanabenz does not cure VWM, which results from genetic mutations affecting eukaryotic initiation factor 2B, a regulator of the cellular stress response targeted by the medication.
Currently, guanabenz is not officially approved by regulatory agencies for VWM treatment. Amsterdam UMC states that patients can only access it within a research setting at this time. An ongoing follow-up study aims to monitor long-term outcomes and evaluate different doses of guanabenz in children from the initial trial. Researchers will assess walking ability, neurological function, brain imaging, safety, and other clinical measures. These new insights offer the first clinical evidence that guanabenz may influence measurable disease progression in children with early-onset VWM, with further long-term research still underway.