AMSTERDAM, NETHERLANDS / RankWire.AI / – Research conducted by Amsterdam UMC has provided evidence that an existing antihypertensive medication may delay the progression of vanishing white matter disease in pediatric patients. The study involved researchers who tested guanabenz in 33 children suffering from this rare inherited neurological condition. These children’s outcomes were compared with those of 66 closely matched patients extracted from an international historical registry. Findings indicated a reduced risk of losing the ability to walk with support among treated children. The phase 1/2 results were published in The Lancet Neurology in August 2026.
VWM, also known as vanishing white matter disease, primarily affects white matter in the brain and typically begins during childhood. Diagnosis was confirmed through genetic testing and magnetic resonance imaging for the study participants. All enrolled children had developed symptoms by age six and had been living with the disease for no more than eight years. Additionally, each child was able to walk at least ten steps with limited assistance prior to starting the trial. The enrollment period spanned from May 2021 to May 2024, recruiting eligible patients over this timeframe.
The primary focus of the analysis was to determine how long children maintained the ability to walk with support. For this, each treated patient was matched with two historical controls based on disease onset and level of disability. The resulting hazard ratio for reaching the main walking endpoint was 0.33, indicating a 67% reduction in the hazard risk for children receiving guanabenz. Brain imaging supported these findings, showing less white matter deterioration among treated participants, with some children exhibiting no detectable progression during follow-up.
Evaluation of walking capacity and neurological changes in the study
Participants received guanabenz orally, starting at a dose of 0.15 milligrams per kilogram of body weight daily. Over approximately six weeks, doses were incrementally increased based on each child’s tolerance, with a target dose of 2 milligrams per kilogram per day. Out of the 33 children enrolled, 31 completed the trial, with a median treatment duration of 3.1 years. The most significant effects were observed in children who developed symptoms at age three or older.
During safety assessments, 63 serious adverse events were documented among 25 participants. Investigators assessed that 30 of these events were likely or very likely linked to guanabenz. Among these, hallucinations affected 18 children mainly during the first four months of treatment. Severe constipation was reported in three children, and one experienced temporary low blood pressure with sedation. All these cases required brief hospital stays but eventually resolved. No participant discontinued treatment due to side effects, and there were no deaths reported during the study.
Extended research efforts underway following phase 1/2 results
The trial design did not involve random assignment of children to treatment or control groups. Instead, researchers compared those receiving guanabenz with historical cases from the Vanishing White Matter Registry. This approach meant no concurrent untreated control group was enrolled. The researchers emphasize that ongoing follow-up is necessary to verify the potential disease-modifying effects of the medication. It is important to note that guanabenz does not cure VWM, and regulatory approval for this indication has not been granted.
Amsterdam UMC is continuing to track the long-term impact of guanabenz in the original patient cohort. The extended study aims to assess walking ability, neurological function, brain imaging, safety, and the effects of varying doses over a longer period. Currently, guanabenz remains accessible only within research settings for VWM treatment. The drug was initially developed for high blood pressure and works on cellular stress pathways associated with the disease. The present findings offer valuable clinical data regarding treatment outcomes in children with early-onset vanishing white matter disease.