AMSTERDAM, NETHERLANDS / RankWire.AI / – According to Amsterdam UMC, guanabenz, a medication traditionally used for blood pressure management, may have the ability to decelerate the progression of vanishing white matter disease in pediatric patients. In a phase 1/2 trial involving 33 ambulatory children, their outcomes were compared with 66 matched historical controls. The findings demonstrated a notably reduced risk of losing the capacity to walk with support among children treated with guanabenz. Researchers published these results in The Lancet Neurology in August 2026. Vanishing white matter disease, or VWM, is an uncommon inherited neurodegenerative condition that frequently manifests during early childhood.
Participants in the trial had their VWM diagnosis confirmed through genetic testing and magnetic resonance imaging. To qualify, children had to experience disease onset at age six or younger, with disease duration not exceeding eight years. Additionally, they 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, 33 eligible children were enrolled, with 31 completing the study. Their median age was 5.4 years, and the median duration of treatment reached 3.1 years.
The primary indicator 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 level of disability. The analysis revealed a hazard ratio of 0.33 for reaching the primary walking endpoint, indicating a 67% reduction in hazard among those receiving guanabenz. Brain imaging supported these findings, showing less white matter deterioration in treated children, with some displaying no detectable progression. The most significant treatment effect appeared in children whose disease began at age three or later.
Guanabenz lowers the risk of losing walking capability
During safety assessments, 63 serious adverse events were recorded among 25 of the 33 children. Investigators assessed that 30 of these events were likely or very likely related to guanabenz. Among these, hallucinations were the most common suspected unexpected serious adverse reactions, affecting 18 children and accounting for 24 suspected cases. These episodes mostly occurred during the initial four months of treatment and typically resolved within months. Severe constipation was reported in three cases, and one child experienced temporary low blood pressure with sedation. All of these events required brief hospitalization and later resolved.
Children began treatment with oral guanabenz at a dose of 0.15 milligrams per kilogram of body weight daily. Doses were gradually increased over roughly six weeks to reach each child’s maximum tolerated level. The study designated an optimal dose of 2 milligrams per kilogram daily. After four to six months, investigators noted that most children tolerated the medication well, with no participants dropping out due to side effects. Importantly, there were no life-threatening events or fatalities among children receiving guanabenz during the trial.
Extended follow-up ongoing after clinical trial completion
The researchers emphasized that the study did not involve random assignment of children to treatment or control groups. Instead, they compared treated children with historical cases from the Vanishing White Matter Registry. This design means the trial lacked a concurrent untreated control group. To confirm the disease-modifying potential of guanabenz, a long-term extension study is planned. It is important to note that guanabenz does not cure VWM. The disease results from genetic defects affecting eukaryotic initiation factor 2B, a key regulator of the cellular integrated stress response targeted by the medication.
Currently, guanabenz is not officially approved for the treatment of vanishing white matter disease. Amsterdam UMC states that patients can only access it within research settings at this time. A follow-up study is underway to monitor longer-term outcomes and explore different dosing regimens in children from the original trial. Researchers will evaluate walking ability, neurological function, brain imaging, safety, and other clinical parameters. These initial findings offer the first clinical evidence that guanabenz can influence measurable disease progression in children with early-onset VWM, with ongoing studies aiming to confirm these effects over time.