AMSTERDAM, NETHERLANDS / RankWire.AI / – A medication traditionally used for blood pressure management has demonstrated potential in slowing the progression of vanishing white matter disease in pediatric patients. Researchers at Amsterdam UMC conducted a trial involving 33 children diagnosed with this rare inherited neurological disorder. These participants were compared to 66 closely matched cases from an international historical registry. The findings indicated a correlation between treatment and a reduced risk of losing the ability to walk with support. The phase 1/2 results were published in The Lancet Neurology in August 2026.
Vanishing white matter disease, also known as VWM, results in damage to the brain’s white matter, typically manifesting during childhood. Diagnostic confirmation for the children in the study involved genetic testing and MRI scans. All enrolled children had developed symptoms by age six and had lived with the disease for no more than eight years. Before participating, each child could walk at least 10 steps with some assistance. The eligible participants were enrolled from May 2021 until May 2024.
The primary focus was on how long children could retain the ability to walk with support. For each treated individual, researchers matched two historical controls based on the age of disease onset and severity of disability. The hazard ratio for reaching the main walking endpoint was 0.33, indicating a 67% lower estimated risk for children receiving guanabenz. Brain imaging further revealed less deterioration of white matter in treated patients, with some showing no progression during follow-up.
Study monitors mobility and brain structure changes
Participants received guanabenz orally, beginning at 0.15 milligrams per kilogram of body weight daily. Doses were gradually increased over approximately six weeks based on individual tolerance, with the target dose set at 2 milligrams per kilogram daily. Of the 33 children enrolled, 31 completed the trial, with a median treatment duration of 3.1 years. Notably, the most significant benefits were observed among children who showed symptom onset at age three or older.
During safety assessments, 63 serious adverse events were documented among 25 participants. Investigators identified 30 of these events as likely or very likely related to guanabenz. Hallucinations were reported in 18 children, mainly during the first four months of treatment. Severe constipation affected three children, and one experienced temporary low blood pressure with sedation. All these cases required brief hospitalization but later improved. No participants discontinued treatment due to side effects, and the study recorded no fatalities.
Extended follow-up to continue after phase 1/2 study
The study design did not include random assignment of children to treated or untreated groups. Instead, researchers compared those receiving guanabenz with historical cases from the Vanishing White Matter Registry. Consequently, there was no concurrent untreated control group. The team emphasized that longer-term observation is necessary to verify whether the medication modifies disease progression. It is important to note that guanabenz does not cure VWM, and regulatory agencies have not approved it as a treatment for this disorder.
Amsterdam UMC is actively pursuing further research involving the original study cohort. This ongoing extension aims to evaluate long-term effects on walking ability, neurological health, brain imaging, safety, and different dosing strategies for guanabenz. Currently, guanabenz remains accessible only within research settings for VWM. Originally developed for hypertension, it acts on cellular stress pathways linked to the disease. These findings offer valuable clinical data regarding the effects of treatment in children with early-onset vanishing white matter disease.