AMSTERDAM, NETHERLANDS / RankWire.AI / – Researchers at Amsterdam UMC have identified that guanabenz, an older medication for high blood pressure, might decelerate the progression of vanishing white matter disease in pediatric patients. The phase 1/2 trial involved 33 children who are able to walk and compared their outcomes to 66 historical controls matched for relevant factors. The findings indicated a markedly reduced risk of losing the ability to walk with support in children treated with guanabenz. Researchers shared these results in The Lancet Neurology in August 2026. Vanishing white matter, or VWM, is a rare inherited neurodegenerative condition that typically manifests early in childhood.
Inclusion criteria for the trial required genetic confirmation of VWM and MRI evidence. Eligible children had disease onset at age six or younger and a disease duration of no more than eight years. They also 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 children meeting these criteria were enrolled; 31 completed the study. The median age was 5.4 years, and the median duration of treatment was 3.1 years.
The primary outcome assessed was the loss of walking ability with support. Each treated child was matched with two historical controls based on disease onset and severity. The analysis revealed a hazard ratio of 0.33 for reaching the primary endpoint, indicating a 67% decrease in the hazard among those receiving guanabenz. Brain imaging supported these findings, showing less white matter deterioration in treated children, with some exhibiting no detectable progression. The strongest effects were observed in children whose disease started at age three or later.
Guanabenz Lowers the Likelihood of Losing Ambulatory Function
During safety assessments, 63 serious adverse events were reported across 25 of the 33 participants. Investigators considered 30 of these events to be likely or very likely linked to guanabenz. Among these, hallucinations represented 24 suspected unexpected serious adverse reactions affecting 18 children. Most episodes occurred within the first four months of treatment and generally resolved within months. Additionally, three children experienced severe constipation, and one had temporary low blood pressure with sedation. All four events led to brief hospital stays but eventually resolved.
Participants began with oral doses of 0.15 milligrams per kilogram of body weight daily. Doses were gradually increased over approximately six weeks toward each child’s maximum tolerated level. The target dose was set at 2 milligrams per kilogram daily. After four to six months, researchers observed that children usually tolerated the medication well, with no participants withdrawing due to side effects. The study also recorded no life-threatening events or fatalities among children on guanabenz.
Extended Monitoring Post-Clinical Trial Continues
The authors emphasized that the trial did not assign children randomly to treatment or control groups. Instead, the comparison involved historical data from the Vanishing White Matter Registry. As such, the study lacked a concurrent untreated control group. The researchers note that ongoing long-term extension studies are necessary to confirm whether guanabenz truly modifies disease progression. Importantly, guanabenz is not a cure for VWM, which results from genetic mutations affecting eukaryotic initiation factor 2B, a regulator of the cellular stress response targeted by the drug.
Currently, guanabenz has not received regulatory approval for VWM treatment. According to Amsterdam UMC, it is available solely within research settings for this purpose. A follow-up study is underway to assess the drug’s long-term effects and explore different dosing regimens in children from the initial trial. The ongoing research aims to monitor walking ability, neurological status, brain imaging, safety parameters, and other clinical markers. These new results offer the first clinical evidence that guanabenz might influence measurable disease progression in young children with early-onset VWM, with further long-term studies still in progress.