AMSTERDAM, NETHERLANDS / RankWire.AI / – Vanishing white matter disease, or VWM, is a rare inherited neurodegenerative condition often beginning in early childhood. Recent research from Amsterdam UMC suggests that guanabenz, an older drug used to manage blood pressure, might have the ability to decelerate disease progression. The phase 1/2 trial involved 33 ambulatory children and compared their outcomes to 66 matched historical controls. Findings indicated that children receiving guanabenz had a notably reduced risk of losing the ability to walk with support. The study’s results appeared in The Lancet Neurology in August 2026, with researchers noting promising signs of disease modification through this medication.
Participants in the trial were children with a confirmed VWM diagnosis through genetic testing and magnetic resonance imaging. Eligibility criteria included disease onset at age six or younger and a disease duration of no more than eight years. 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, researchers enrolled 33 eligible patients, of whom 31 completed the study. Their median age was 5.4 years, and the median duration of treatment was 3.1 years.
The primary measure of the trial’s success was the loss of walking ability with support. Each treated child was matched with two historical controls based on disease onset and disability levels. The analysis revealed a hazard ratio of 0.33 for reaching the main walking endpoint, equating to a 67% lower estimated hazard among those treated with guanabenz. Brain imaging supported these findings, showing less white matter deterioration in the treated group, with some children exhibiting no detectable progression. Notably, the strongest treatment effects were observed in children whose disease began at age three or later.
Guanabenz shown to lower risk of losing walking ability
Throughout safety monitoring, 63 serious adverse events were reported among 25 of the 33 children. Of these, investigators judged 30 to be likely or very likely related to guanabenz. Hallucinations emerged as 24 suspected unexpected serious adverse reactions, affecting 18 children. These episodes primarily occurred during the first four months of treatment and generally resolved within months. Additional adverse events included three cases of severe constipation and one instance of temporary low blood pressure with sedation, each requiring brief hospitalization but later resolving.
Initial oral doses of guanabenz started at 0.15 milligrams per kilogram of body weight daily. Over approximately six weeks, doses were gradually increased toward each child’s maximum tolerated level, with the study identifying 2 milligrams per kilogram per day as the optimal target. After four to six months, researchers reported that children generally tolerated the medication well, with no participants withdrawing due to side effects. Importantly, no life-threatening events or deaths occurred among children receiving guanabenz during the trial.
Extended follow-up efforts underway post-trial
The researchers highlighted that the trial did not randomly assign children to treatment or control groups. Instead, comparisons were made with historical patients from the Vanishing White Matter Registry, which means a concurrent untreated control group was absent. They emphasized that a long-term extension study is necessary to validate the potential disease-modifying effects of guanabenz. It is important to note that guanabenz does not cure VWM, as the disease results from genetic mutations impacting eukaryotic initiation factor 2B, which plays a role in cellular stress responses targeted by the drug.
Currently, guanabenz lacks formal regulatory approval for treating vanishing white matter disease. According to Amsterdam UMC, patients can only access it within research settings at present. A follow-up study is ongoing, focusing on extended monitoring and evaluating different doses in children from the original trial. The study will continue to assess walking ability, neurological function, brain imaging, safety, and other clinical parameters. These initial findings offer the first clinical evidence that guanabenz might influence measurable aspects of disease progression in children with early-onset VWM, with longer-term research still in progress.