AMSTERDAM, NETHERLANDS / RankWire.AI / – A team at Amsterdam UMC has indicated that guanabenz, an older medication used for blood pressure, could potentially decelerate the progression of vanishing white matter disease in pediatric patients. The phase 1/2 trial involved 33 children who are ambulatory and compared their outcomes with 66 historical controls matched for key characteristics. The findings revealed a notably reduced risk of losing the ability to walk with support among children treated with guanabenz. Researchers shared their results in The Lancet Neurology in August 2026. Vanishing white matter disease, or VWM, is a rare inherited neurodegenerative condition that often manifests early in childhood.
The trial’s inclusion criteria mandated a confirmed diagnosis of VWM through genetic testing and magnetic resonance imaging. Eligible children had disease onset at age six or younger, with disease duration not exceeding eight years. Participants 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, 33 eligible children were enrolled, 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 for assessing the efficacy of treatment was the loss of walking ability with support. To analyze results, each treated participant was matched with two untreated historical controls based on disease onset and disability level. The hazard ratio for reaching the primary walking endpoint was calculated at 0.33, indicating a 67% lower estimated hazard among those receiving guanabenz. Brain imaging supported these findings, revealing less white matter deterioration, with some children showing no detectable disease progression. Notably, the strongest effects appeared in children whose disease began at age three or later.
Guanabenz reduces the likelihood of losing walking ability
During safety assessments, 63 serious adverse events were reported among 25 of the 33 children. Of these, investigators considered 30 events to be likely or very likely related to guanabenz. Hallucinations were prominent, accounting for 24 suspected unexpected serious adverse reactions affecting 18 children. These episodes mostly occurred during the initial four months of treatment and generally resolved within months of onset. Severe constipation was reported in three cases, while one child experienced temporary low blood pressure with sedation; all four events required brief hospitalization and later resolved.
The initial dosage was set at 0.15 milligrams per kilogram of body weight daily, administered orally. Researchers increased doses over approximately six weeks up to each child’s maximum tolerated level, with an optimal target dose of 2 milligrams per kilogram daily. After the first four to six months, children generally tolerated the medication well, with no participants dropping out due to side effects. The trial recorded no life-threatening incidents or deaths among children receiving guanabenz.
Ongoing long-term monitoring post-trial
The researchers emphasized that the study did not randomly assign children to treatment or control groups. Instead, the comparison was made with historical patients from the Vanishing White Matter Registry, which means a concurrent untreated control group was absent. They noted that a long-term extension study is necessary to verify the potential disease-modifying effects of guanabenz. It is important to note that guanabenz does not cure VWM. The disease results from genetic defects affecting eukaryotic initiation factor 2B, a protein that regulates the cellular integrated stress response targeted by the medication.
Currently, guanabenz lacks regulatory approval specifically for vanishing white matter disease. According to Amsterdam UMC, patients can access it for VWM only within a research setting at this time. A follow-up study is underway, focusing on longer-term effects and testing different dosing regimens of guanabenz in children from the original trial. Researchers will monitor walking ability, neurological function, brain imaging, safety and other clinical measures. These initial findings provide the first clinical evidence that guanabenz may influence measurable disease progression in children with early-onset VWM, with further research ongoing.