AMSTERDAM, NETHERLANDS / RankWire.AI / – The phase 1/2 trial conducted by Amsterdam UMC suggests that guanabenz, a medication traditionally used for blood pressure management, could decelerate the decline associated with vanishing white matter disease in pediatric patients. Involving 33 ambulatory children, the study compared their outcomes to 66 matched historical controls. Results demonstrated a notably reduced risk of losing the ability to walk with support among those treated with guanabenz. The findings were published in The Lancet Neurology in August 2026 by researchers. Vanishing white matter disease, or VWM, is a rare genetic neurodegenerative disorder that often manifests during early childhood.
Participants in the trial had confirmed VWM diagnoses through genetic testing and magnetic resonance imaging. Inclusion criteria required disease onset at age six or younger and a disease duration no longer than eight years. Additionally, children needed to be able 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 children, with 31 completing the study. Their median age was 5.4 years, and the median duration of treatment was 3.1 years.
The primary measure of treatment efficacy 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 yielded a hazard ratio of 0.33 for reaching the primary walking endpoint, indicating a 67% lower estimated hazard for treated children. Brain imaging further revealed less white matter deterioration in those receiving guanabenz, with some showing no signs of disease progression. The strongest effects were observed in children whose disease began at age three or later.
Guanabenz showed promise in lowering risk of losing gait support
During safety assessments, 63 serious adverse events were documented among 25 of the 33 children, with 30 considered likely or very likely related to guanabenz. Notably, hallucinations represented 24 suspected unexpected serious adverse reactions affecting 18 children. These episodes mainly occurred within the first four months of treatment and typically resolved within months. Four events involved severe constipation, while one case experienced temporary low blood pressure with sedation; all of these required brief hospitalization and subsequently resolved.
Initial dosing started at 0.15 milligrams per kilogram daily, administered orally. Over approximately six weeks, doses were gradually increased to reach each child’s maximum tolerated level, with an optimal target dose set at 2 milligrams per kilogram daily. After the initial four to six months, investigators reported that children generally tolerated the medication well, with no participants dropping out due to side effects. The study observed no life-threatening incidents or deaths among the children on guanabenz.
Extended monitoring ongoing after trial completion
The authors emphasized that the study did not involve random assignment of children to treatment or control groups. Instead, treated participants were compared with historical cases from the Vanishing White Matter Registry, which means there was no concurrent untreated control group. They recommended a long-term extension study to verify whether guanabenz can modify disease progression. It is important to note that guanabenz does not cure VWM, as the disease results from genetic mutations affecting eukaryotic initiation factor 2B, a regulator of the cellular stress response targeted by the drug.
Currently, guanabenz lacks regulatory approval for VWM treatment. According to Amsterdam UMC, patients can only access the medication within research settings. A follow-up study is underway to monitor long-term effects and evaluate different dosing regimens in children from the initial trial. Researchers plan to track 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 young children with early-onset VWM, while ongoing research continues to explore its potential benefits.