AMSTERDAM, NETHERLANDS / RankWire.AI / – According to Amsterdam UMC, guanabenz, an established medication for high blood pressure, shows potential in slowing the progression of vanishing white matter disease in pediatric patients. The phase 1/2 study involved 33 children who could walk independently or with support, and compared their outcomes with 66 historical controls matched for disease characteristics. The findings indicated a notably reduced risk of losing the ability to walk with support among those treated with guanabenz. Researchers published the results in The Lancet Neurology in August 2026. Vanishing white matter disease, or VWM, is a rare inherited neurodegenerative disorder that often manifests during early childhood.
The study included children with confirmed VWM diagnoses through genetic testing and MRI scans. Participants were eligible if their disease onset was at age six or younger and their disease duration did not exceed eight years. The children 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 who met these criteria were enrolled, 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 of treatment success was the preservation of walking ability with support. Each child receiving guanabenz was matched with two untreated historical controls based on disease onset and level of disability. The analysis revealed a hazard ratio of 0.33 for reaching the main walking endpoint, indicating a 67% lower estimated risk among the treated group. Brain imaging supported these findings, showing less white matter deterioration in children receiving treatment, with some exhibiting no detectable progression. The strongest treatment effect was observed in children whose disease began at age three or later.
Guanabenz appears to lower the chance of losing mobility
Throughout the trial, safety monitoring documented 63 serious adverse events among 25 of the 33 children. Of these, investigators considered 30 events as likely or very likely related to guanabenz. Notably, hallucinations were suspected in 24 cases, affecting 18 children, primarily during the first four months of treatment, with most resolving within months of onset. Four children experienced severe constipation, and one experienced temporary hypotension with sedation; all four events led to brief hospital stays and subsequently resolved.
Participants initially received oral guanabenz at 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 study aimed for an optimal dose of 2 milligrams per kilogram per day. After four to six months, investigators observed that children generally tolerated the medication well, with no participants withdrawing due to side effects. No life-threatening incidents or deaths occurred during the trial among children on guanabenz.
Ongoing long-term follow-up after the clinical trial
The researchers emphasized that the trial did not utilize random assignment. Instead, they compared treated children with historical data from the Vanishing White Matter Registry. This design meant there was no concurrent untreated control group. The team indicated that a long-term extension study is necessary to verify the potential disease-modifying effects. It is important to note that guanabenz does not cure VWM, which results from genetic mutations affecting eukaryotic initiation factor 2B, a key regulator of the cellular stress response targeted by the medication.
Currently, guanabenz lacks formal regulatory approval for VWM treatment. Amsterdam UMC states that it is accessible to patients only within research settings. A follow-up study is underway to monitor long-term outcomes and test different dosing regimens of guanabenz in children from the original trial. Researchers will evaluate walking ability, neurological function, brain imaging results, safety concerns, and other clinical parameters. These initial clinical findings offer evidence that guanabenz may influence disease progression in children with early-onset VWM, with further long-term research ongoing.