AMSTERDAM, NETHERLANDS / RankWire.AI / – In Amsterdam, during the period from May 2021 to May 2024, researchers at Amsterdam UMC conducted a study indicating that guanabenz, a longstanding medication for blood pressure, could potentially decelerate the decline associated with vanishing white matter disease in pediatric patients. The phase 1/2 investigation involved monitoring 33 children who could walk and comparing their outcomes to 66 historical controls matched on key characteristics. The findings revealed a notably reduced risk of losing the ability to ambulate with support among those treated with guanabenz. Researchers shared these results in The Lancet Neurology in August 2026. Vanishing white matter, or VWM, is an uncommon inherited neurodegenerative condition that frequently manifests during early childhood.
Participants were selected based on confirmed VWM diagnosis through genetic testing and magnetic resonance imaging. Criteria included disease onset at age six or younger and a disease duration not exceeding eight years. To qualify, children 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; 31 completed the trial. Their median age was 5.4 years, and they were on treatment for a median of 3.1 years.
The main measure for assessing treatment impact 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 yielded a hazard ratio of 0.33 for the primary walking endpoint, indicating a 67% lower estimated hazard among treated individuals. Brain imaging further supported these findings, showing less white matter deterioration in treated children, with some exhibiting no detectable progression. The strongest treatment effects appeared in children whose disease began at age three or later.
Guanabenz Demonstrates Potential in Reducing Walking Decline
Throughout safety assessments, 63 serious adverse events were documented among 25 of the 33 participants. Investigators considered 30 of these events as likely or very likely linked to guanabenz. Among these, hallucinations were reported as 24 suspected unexpected serious adverse reactions affecting 18 children. These episodes mostly occurred during the first four months of treatment and generally resolved within months. Four cases involved severe constipation, and one involved temporary low blood pressure with sedation; all required brief hospital stays and later resolved.
Children began treatment with oral guanabenz at 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 set at 2 milligrams per kilogram daily. After four to six months, investigators reported that most children tolerated the treatment well. No participants discontinued due to side effects, and there were no life-threatening events or fatalities among children receiving guanabenz.
Extended Follow-Up Continues Post-Study
The study authors emphasized that the trial did not randomly assign children to treatment or control groups. Instead, they compared treated children to historical patients from the Vanishing White Matter Registry, meaning there was no concurrent untreated control group. They noted that a long-term extension study is necessary to confirm the potential disease-modifying effects. Importantly, guanabenz does not cure VWM, which results from genetic mutations affecting eukaryotic initiation factor 2B that regulate the cellular stress response targeted by the drug.
Currently, guanabenz lacks regulatory approval for VWM treatment. Amsterdam UMC states that patients can only access the medication within research settings at present. A follow-up study is underway to monitor long-term effects and test different doses of guanabenz in children from the original trial. The researchers plan to assess walking ability, neurological function, brain imaging, safety metrics, and other clinical indicators. These initial findings mark the first clinical evidence that guanabenz might influence disease progression in children with early-onset VWM, with ongoing research to confirm its potential benefits over time.