AMSTERDAM, NETHERLANDS / RankWire.AI / – A study conducted by Amsterdam UMC indicates that guanabenz, an older medication for blood pressure, might slow the progression of vanishing white matter disease in pediatric patients. The phase 1/2 trial observed 33 ambulatory children and compared their outcomes with 66 historical controls matched by relevant factors. The findings demonstrated a notably reduced risk of losing the ability to walk with support in children treated with guanabenz. Researchers published these results in The Lancet Neurology in August 2026. Vanishing white matter disease, or VWM, is a rare inherited neurodegenerative disorder that typically manifests during early childhood.
Children included in the trial had confirmed VWM diagnoses through genetic testing and magnetic resonance imaging. To qualify, their disease onset had to occur at age six or younger, with disease duration not exceeding eight years. They also needed to walk at least 10 steps with only light support from one hand. Between May 31, 2021, and May 31, 2024, researchers enrolled 33 eligible participants, with 31 completing the study. The median age was 5.4 years, and the median treatment duration reached 3.1 years.
The primary measure of treatment success was the preservation of walking ability with support. Each treated child was matched with two historical controls based on disease onset and level of disability. The analysis yielded a hazard ratio of 0.33 for reaching the primary walking endpoint, indicating a 67% reduction in the estimated hazard among those receiving guanabenz. Brain imaging also revealed less white matter deterioration in the treated group, with some showing no detectable progression at all. The strongest treatment effects appeared among children whose disease began at age three or later.
Guanabenz shows promise in reducing risk of losing mobility
During safety assessments, 63 serious adverse events were documented among 25 of the 33 children. Investigators assessed 30 of these incidents as likely or very likely related to guanabenz. Notably, hallucinations were identified as 24 suspected unexpected serious adverse reactions, affecting 18 children. These episodes primarily occurred within the first four months of treatment and generally subsided within months of onset. Severe constipation affected three children, while one experienced temporary low blood pressure with sedation, each requiring brief hospitalization but later resolving.
Initially, participants received oral guanabenz at 0.15 milligrams per kilogram of body weight daily. Doses were then gradually increased over approximately six weeks toward each child’s maximum tolerated dose. The targeted dose was set at 2 milligrams per kilogram daily. After four to six months, investigators reported that children generally tolerated the medication well, with no participants withdrawing due to side effects. Importantly, no life-threatening events or deaths occurred among children treated with guanabenz.
Extended follow-up to continue beyond clinical trial phase
The researchers emphasized that the trial did not involve random assignment of children to treatment or control groups. Instead, the comparison was made against historical patients from the Vanishing White Matter Registry, which meant there was no concurrent untreated control group. They indicated that a long-term extension study is necessary to confirm the potential disease-modifying effects. It is important to note that guanabenz does not cure VWM, as the disorder results from genetic mutations affecting eukaryotic initiation factor 2B, which regulates the cellular integrated stress response targeted by the drug.
Currently, guanabenz lacks regulatory approval for the treatment of vanishing white matter disease. According to Amsterdam UMC, access to the drug for VWM is limited to research settings at present. A follow-up study is ongoing to monitor long-term outcomes and evaluate different guanabenz dosages in children from the initial trial. This research will track various measures, including walking ability, neurological function, brain imaging, safety, and other clinical parameters. These emerging findings offer the first clinical evidence that guanabenz may influence observable disease progression in children with early-onset VWM, as further long-term research progresses.