AMSTERDAM, NETHERLANDS / RankWire.AI / – Amsterdam UMC reports that the blood pressure medication guanabenz, an older drug, shows potential to slow the progression of vanishing white matter disease in children. The phase 1/2 trial involved 33 ambulatory children and compared their outcomes with 66 matched historical controls. Results demonstrated a significantly 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 inherited neurodegenerative disorder that commonly manifests during early childhood.
The study included children with VWM confirmed through genetic testing and MRI scans. Eligibility criteria required disease onset at age six or younger and a disease duration not exceeding eight years. Participants had 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 duration of treatment was 3.1 years.
The primary measure of treatment effectiveness was the loss of walking ability with support. Each treated child was matched with two historical controls based on age at disease onset and level of disability. The analysis yielded a hazard ratio of 0.33 for reaching the main walking endpoint, indicating a 67% lower estimated hazard in treated patients. Brain imaging also revealed less white matter deterioration among those receiving guanabenz, with some showing no detectable progression. The most pronounced treatment effect was observed in children whose disease started at age three or later.
Guanabenz lowers risk of losing walking function
Throughout safety monitoring, 63 serious adverse events were documented among 25 of the 33 children. Investigators considered 30 of these events as likely or very likely related to guanabenz. Hallucinations accounted for 24 suspected unexpected serious adverse reactions, affecting 18 children. These episodes primarily occurred during the initial four months of treatment and generally resolved within months. Three instances involved severe constipation, and one involved temporary low blood pressure with sedation. All four cases necessitated brief hospital stays, and each resolved later.
Initial dosing of oral guanabenz was 0.15 milligrams per kilogram daily. Researchers gradually increased doses over approximately six weeks toward each child’s maximum tolerated level. The target dose was set at 2 milligrams per kilogram per day. After four to six months, investigators observed that children generally tolerated the medication well. No participants withdrew due to side effects, and no life-threatening events or deaths occurred among children receiving guanabenz during the trial.
Extended follow-up underway post-trial
The researchers emphasized that the trial did not randomly assign children to treatment and control groups. Instead, they compared treated children with historical cases from the Vanishing White Matter Registry, which meant there was no concurrent untreated control group. They indicated that a long-term extension study should 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 drug.
Guanabenz has not received regulatory approval for the treatment of vanishing white matter disease. According to Amsterdam UMC, patients can currently access the medication only within a research context. A follow-up study continues with longer-term monitoring and investigates different doses in children from the original trial. Researchers will assess walking ability, neurological function, brain imaging, safety, and other clinical endpoints. These new findings constitute the first clinical evidence that guanabenz may influence measurable disease progression in children with early-onset VWM, as longer-term research progresses.