AMSTERDAM, NETHERLANDS / RankWire.AI / – Researchers at Amsterdam UMC have reported that guanabenz, a medication originally used for high blood pressure, could potentially decelerate the progression of vanishing white matter disease in pediatric cases. The phase 1/2 trial involved 33 children who were ambulatory and compared their outcomes with 66 matched historical controls. The study found that children receiving guanabenz had a markedly reduced risk of losing their ability to walk with support. Researchers shared the findings in The Lancet Neurology in August 2026. Vanishing white matter disease, or VWM, is an uncommon inherited neurodegenerative condition that frequently begins during early childhood.
The study included children whose diagnosis of VWM was confirmed via genetic testing and magnetic resonance imaging. Eligibility criteria required disease onset at age six or younger and a disease duration not exceeding eight years. Participants 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 suitable children, with 31 completing the trial. Their median age was 5.4 years, and the median duration of treatment was 3.1 years.
The primary measure for assessing treatment efficacy was the loss of walking ability with support. Each treated child was matched with two historical controls who had similar disease onset and disability levels. The analysis revealed a hazard ratio of 0.33 for reaching the main walking endpoint, indicating a 67% lower estimated hazard in treated patients. Brain imaging further supported these findings, showing less white matter deterioration among treated children, with some displaying no detectable progression at all. The most notable treatment effect was observed in children whose disease began at age three or later.
Guanabenz shows potential in decreasing risk of mobility loss
Safety monitoring recorded 63 serious adverse events among 25 of the 33 children. Investigators assessed 30 of these events as likely or very likely related to guanabenz. Among these, hallucinations accounted for 24 suspected unexpected serious adverse reactions affecting 18 children. These episodes mainly occurred during the first four months of treatment and generally resolved within months. Three cases involved severe constipation, and one case involved temporary low blood pressure with sedation. All four events required brief hospitalization and eventually resolved.
Participants started on oral guanabenz at a dose of 0.15 milligrams per kilogram of body weight daily. Researchers gradually increased doses over approximately six weeks to reach each child’s maximum tolerated dose. The study targeted an optimal dose of 2 milligrams per kilogram daily. After four to six months, investigators reported that children generally tolerated the treatment well. No participant withdrew due to side effects. The trial also recorded no life-threatening events or deaths among children receiving guanabenz.
Extended follow-up continues beyond the initial clinical trial phase
The researchers cautioned that the study design did not involve random assignment to treatment and control groups. Instead, they compared treated children with historical cases from the Vanishing White Matter Registry. This approach means there was no concurrent untreated control group. The team emphasized that a long-term extension study is needed to verify the potential disease-modifying effects. It is important to note that guanabenz does not cure VWM. The disorder results from genetic defects affecting eukaryotic initiation factor 2B, a key regulator of the cellular integrated 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 a research setting at this time. A follow-up study is ongoing, focusing on longer-term monitoring and testing different doses of guanabenz in children from the original trial. Researchers aim to evaluate walking ability, neurological function, brain imaging, safety measures, and other clinical endpoints. These initial findings provide evidence that guanabenz might influence measurable aspects of disease progression in children with early-onset VWM, with longer-term research still underway.