AMSTERDAM, NETHERLANDS / RankWire.AI / – Researchers at Amsterdam UMC have reported that guanabenz, an older medication used for blood pressure management, might slow the progression of vanishing white matter disease in pediatric patients. The phase 1/2 clinical trial involved 33 children who could walk independently and compared their outcomes to 66 matched historical controls. The findings indicated that children treated with guanabenz faced a significantly reduced risk of losing the ability to walk with support. The results were published in The Lancet Neurology in August 2026 by researchers. Vanishing white matter disease, or VWM, is a rare inherited neurodegenerative condition that typically manifests during early childhood.
Participants in the study were children with confirmed VWM diagnoses through genetic testing and magnetic resonance imaging. Inclusion criteria required disease onset at age six or younger and a maximum disease duration of eight years. These children also 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 eligible patients were enrolled, with 31 completing the trial. Their median age was 5.4 years, and the median treatment duration was 3.1 years.
The primary outcome measure 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 reaching the primary walking endpoint, indicating a 67% lower estimated hazard among those receiving guanabenz. Brain imaging also revealed that treated children experienced less white matter deterioration, with some showing no detectable disease progression. The most notable treatment effect was observed in children whose disease started at age three or later.
Guanabenz Demonstrates Potential to Reduce Walking Loss Risk
Throughout safety monitoring, 63 serious adverse events were reported among 25 of the 33 children. Of these, investigators considered 30 events as likely or very likely related to guanabenz. Hallucinations accounted for 24 suspected unexpected serious adverse reactions affecting 18 children, mostly occurring during the first four months of treatment and generally resolving within months. Four cases involved severe constipation, and one involved temporary low blood pressure with sedation. All four of these events required brief hospitalization and eventually resolved.
Children started oral guanabenz at a dose of 0.15 milligrams per kilogram of body weight daily, with doses gradually increased over roughly six weeks to each child’s maximum tolerated level. The study aimed for a target dose of 2 milligrams per kilogram per day. After four to six months, investigators reported that the children generally tolerated the medication well, with no participants withdrawing due to side effects. No life-threatening events or deaths were recorded among children on guanabenz during the trial.
Extended Observation Continues Beyond the Initial Trial
The authors highlighted that the study was not a randomized controlled trial; instead, it compared treated patients with historical cases from the Vanishing White Matter Registry. As a result, there was no concurrent untreated control group. The researchers emphasized that a long-term extension study is needed to verify whether guanabenz can modify disease progression. It is also important to note that guanabenz does not cure VWM, which results from genetic mutations affecting eukaryotic initiation factor 2B—a key regulator of the cellular stress response targeted by the drug.
Guanabenz currently lacks regulatory approval for VWM treatment, and Amsterdam UMC states that it is available for VWM only within research settings at this time. A follow-up study is underway to monitor long-term outcomes and evaluate different dosing regimens in children from the original trial. This ongoing research will assess walking ability, neurological functions, brain imaging, safety, and other clinical parameters. The emerging data provide the first clinical evidence that guanabenz can influence measurable disease progression in early-onset VWM, with longer-term studies still in progress.