AMSTERDAM, NETHERLANDS / RankWire.AI / – Researchers at Amsterdam UMC have reported that guanabenz, a well-established antihypertensive medication, might decelerate the progression of vanishing white matter disease in children. The phase 1/2 trial monitored 33 children living with the condition who were ambulatory and compared their outcomes with 66 matched historical controls. The findings indicated a notable reduction in the risk of losing the ability to walk with support among those treated with guanabenz. Researchers published their results in The Lancet Neurology in August 2026. VWM, or vanishing white matter disease, is an infrequent inherited neurodegenerative disorder that typically manifests early in childhood.
The study population included children whose VWM diagnosis was confirmed through genetic analysis and magnetic resonance imaging. To qualify, participants had to experience disease onset at age six or younger and have a disease duration no longer than eight years. Additionally, children needed to be able to walk at least 10 steps with minimal support from one hand. Between May 31, 2021, and May 31, 2024, researchers enrolled 33 eligible children, with 31 completing the trial. The median age was 5.4 years, and the median duration of treatment was 3.1 years.
The primary measure of treatment effectiveness was the loss of walking ability with support. Each treated child was matched with two historical controls based on disease onset and disability severity. The analysis revealed a hazard ratio of 0.33 for reaching the primary walking endpoint, indicating a 67% lower hazard among the treated group. Brain imaging further demonstrated that children receiving guanabenz experienced less white matter deterioration, with some showing no detectable progression. The most significant treatment effect was observed in children whose disease began at age three or later.
Guanabenz shows promise in reducing risk of mobility loss
Throughout safety monitoring, 63 serious adverse events were documented among 25 of the 33 participants. Investigators assessed 30 of these events as likely or very likely related to guanabenz. Hallucinations emerged as 24 suspected unexpected serious adverse reactions, affecting 18 children. These episodes primarily occurred within the first four months of treatment and typically resolved within months. Four cases involved severe constipation, and one case involved temporary hypotension with sedation; all four required brief hospitalization and subsequently resolved.
Children started on oral guanabenz at a dose of 0.15 milligrams per kilogram of body weight daily, with dose escalation over approximately six weeks to reach each child’s maximum tolerated level. The target dose was set at 2 milligrams per kilogram per day. After four to six months, investigators reported that most children tolerated the medication well, with no participants withdrawing due to side effects. There were no life-threatening events or deaths in the guanabenz-treated group during the trial.
Ongoing long-term assessment after clinical trial
The researchers emphasized that the trial did not involve random assignment of children to treatment and control groups. Instead, comparisons were made with historical patients from the Vanishing White Matter Registry, which means there was no concurrent untreated control group. They noted that a long-term extension study is necessary to confirm the potential disease-modifying effects. It is also important to recognize that guanabenz does not cure VWM, which results from genetic mutations affecting eukaryotic initiation factor 2B, a regulator of the cellular integrated stress response targeted by this medication.
Currently, guanabenz is not approved by regulatory agencies for the treatment of vanishing white matter disease. According to Amsterdam UMC, the drug is accessible for VWM only within research settings at this stage. A follow-up study is underway, focusing on extended monitoring and testing different guanabenz doses in children from the initial trial. Researchers will evaluate walking ability, neurological function, brain imaging, safety, and other clinical parameters. The new data provide the first clinical evidence that guanabenz has the potential to alter measurable disease progression in children with early-onset VWM, as longer-term research continues to develop.