AMSTERDAM, NETHERLANDS / RankWire.AI / – A team at Amsterdam UMC has found that guanabenz, an established medication for blood pressure, might slow the progression of vanishing white matter disease in pediatric patients. The phase 1/2 trial involved 33 children who could walk and compared their outcomes to 66 historical controls with similar profiles. Results indicated a notably reduced risk of losing the ability to walk with support among those treated with guanabenz. Researchers shared their findings in The Lancet Neurology in August 2026. Vanishing white matter, or VWM, is an uncommon inherited neurodegenerative disorder typically manifesting early in childhood.
Participants in the trial were children with confirmed VWM diagnoses verified through genetic testing and MRI scans. The inclusion criteria mandated disease onset at age six or younger and a disease duration no longer than eight years. The children had to be capable of walking at least 10 steps with minimal support from one hand. Between May 31, 2021, and May 31, 2024, researchers recruited 33 eligible children, with 31 completing the study. Their median age was 5.4 years, and the median treatment duration was 3.1 years.
The primary measure of effectiveness was the loss of walking ability with support. To evaluate this, each treated child was matched with two historical controls based on disease onset and disability levels. The hazard ratio for reaching the primary walking endpoint was calculated at 0.33, indicating a 67% reduction in the risk for treated patients. Brain imaging also revealed less white matter deterioration among children receiving guanabenz, with some showing no detectable progression. The most significant treatment effects were observed in children whose disease began at age three or later.
Guanabenz Demonstrates Potential to Lower Risk of Walking Decline
Throughout safety monitoring, 63 serious adverse events were reported in 25 of the 33 participants. Investigators identified 30 of these events as likely or very likely related to guanabenz. Hallucinations were noted as 24 suspected unexpected serious adverse reactions, affecting 18 children. These episodes mainly took place within the first four months of therapy and generally resolved within months of onset. Four cases involved severe constipation, while one case involved temporary low blood pressure with sedation. All four incidents resulted in brief hospital stays and later resolved.
Participants initiated treatment with oral guanabenz at 0.15 milligrams per kilogram daily. Doses were gradually increased over about six weeks to reach each child’s maximum tolerated level. The study aimed for an optimal dose of 2 milligrams per kilogram daily. After four to six months, researchers reported that most children tolerated the medication well, with no withdrawals due to side effects. Importantly, no life-threatening events or fatalities occurred among the children receiving guanabenz.
Extended Follow-Up Continues Post-Study
The researchers emphasized that the trial was not randomized. Instead, treated children were compared to historical patients from the Vanishing White Matter Registry. Because of this design, the study lacked a concurrent untreated control group. To verify the disease-modifying potential, 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—an element involved in cellular stress response pathways targeted by the drug.
Currently, guanabenz is not approved for VWM treatment by regulatory agencies. According to Amsterdam UMC, it is accessible only within research settings at present. A follow-up study is ongoing, focusing on longer-term effects and testing different dosing strategies in children from the original trial. The study will assess walking ability, neurological functions, brain imaging, safety metrics, and other clinical parameters. These initial findings mark the first clinical evidence suggesting guanabenz can influence disease progression in children with early-onset VWM, with ongoing research further exploring its potential.