AMSTERDAM, NETHERLANDS / RankWire.AI / – A study conducted by Amsterdam UMC indicates that guanabenz, a longstanding antihypertensive medication, could potentially slow the progression of vanishing white matter disease in pediatric patients. The phase 1/2 trial monitored 33 children who could walk and compared their outcomes to 66 matched historical controls. Results demonstrated a notably reduced risk of losing the ability to walk with support among children treated with guanabenz. Researchers published their findings in The Lancet Neurology in August 2026. Vanishing white matter disease, or VWM, is a rare genetic neurodegenerative disorder that typically manifests during early childhood.
The study included children with confirmed VWM diagnoses through genetic testing and MRI scans. Eligibility criteria required disease onset at age six or younger and a disease duration of no more than eight years. Participants 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 trial. Their median age was 5.4 years, and the median treatment duration was 3.1 years.
The primary efficacy measure was the loss of walking ability with support. Each treated participant was matched with two historical controls based on disease onset and disability level. The analysis yielded a hazard ratio of 0.33 for reaching the main walking endpoint, translating to a 67% reduction in hazard for treated children. Brain imaging further supported these findings, showing less white matter deterioration in the treated group, with some children displaying no detectable progression. The most pronounced treatment benefits were observed in children whose disease began at age three or later.
Guanabenz demonstrates potential in lowering risk of mobility loss
Monitoring for safety recorded 63 serious adverse events among 25 of the 33 participants. Investigators considered 30 of these events as likely or very likely related to guanabenz. Notably, hallucinations were reported as 24 suspected unexpected serious adverse reactions, affecting 18 children. These episodes mostly occurred within the first four months of treatment and generally resolved within months. Severe constipation was observed in three cases, and one participant experienced temporary low blood pressure with sedation. All four events required brief hospitalization and eventually resolved.
Participants commenced oral guanabenz at a dose of 0.15 milligrams per kilogram daily. Over approximately six weeks, doses were gradually increased to reach each child’s maximum tolerated level, with an target dose of 2 milligrams per kilogram daily. After the initial four to six months, investigators observed that children generally tolerated the treatment well. No participants withdrew due to side effects, and there were no life-threatening incidents or fatalities during the trial among those receiving guanabenz.
Extended monitoring ongoing following the clinical trial
The authors emphasized that the trial did not involve random assignment of children to treatment and control groups. Instead, treated children were compared with historical patients from the Vanishing White Matter Registry. This design means the study lacked a concurrent untreated control group. To confirm the potential disease-modifying effects, a long-term extension study is planned. It’s important to note that guanabenz does not cure VWM, which results from genetic mutations affecting eukaryotic initiation factor 2B that governs the cellular stress response targeted by the drug.
Currently, guanabenz is not approved by regulators for VWM treatment. Amsterdam UMC states that patients can only access the medication within research settings at this stage. A follow-up study is underway to evaluate longer-term effects and different dosing regimens in children from the original cohort. Researchers aim to monitor walking ability, neurological function, brain imaging, safety and other clinical outcomes. These initial findings mark the first clinical evidence that guanabenz might influence disease progression in young children with early-onset VWM, with further investigation ongoing.