AMSTERDAM, NETHERLANDS / RankWire.AI / – Evidence suggests that an existing antihypertensive medication may slow the progression of vanishing white matter disease in pediatric patients. Researchers at Amsterdam UMC evaluated guanabenz in a cohort of 33 children diagnosed with this rare inherited neurological condition. These patients were compared with 66 closely matched cases from an international historical registry. The study found that treatment was associated with a reduced risk of losing the ability to walk with support. Results from the phase 1/2 study were published in The Lancet Neurology in August 2026.
Vanishing white matter disease, also known as VWM, affects the brain’s white matter and generally manifests during childhood. Diagnosis was confirmed through genetic testing and magnetic resonance imaging in all enrolled children. Participants had developed symptoms by age six and had been living with the disease for no more than eight years. Prior to the trial, each child was able to walk at least 10 steps with some assistance. Eligible patients were enrolled between May 2021 and May 2024.
The primary outcome focused on the duration children retained the ability to walk with support. Each treated patient was matched with two historical controls based on disease onset and disability level. The hazard ratio for reaching the primary walking endpoint was 0.33, indicating a 67% decrease in the estimated hazard for children treated with guanabenz. Brain imaging supported these findings, revealing less white matter deterioration among treated participants, with some experiencing no detectable progression during follow-up.
Study monitors locomotor function and brain changes
Guanabenz was administered orally at an initial dose of 0.15 milligrams per kilogram of body weight daily. Doses were gradually increased over approximately six weeks based on individual tolerance, with a target dose set at 2 milligrams per kilogram per day. Of the 33 children enrolled, 31 completed the trial, with a median treatment duration of 3.1 years. The most significant treatment effects were observed in children whose symptoms started at age three or older.
Throughout the study, safety assessments recorded 63 serious adverse events among 25 participants. Investigators attributed 30 of these events as likely or very likely related to guanabenz. Notably, 18 children experienced hallucinations mostly during the first four months of therapy. Three children had severe constipation, and one experienced temporary low blood pressure with sedation. All these events required brief hospitalization but resolved later. No participant discontinued treatment due to side effects, and there were no fatalities reported during the trial.
Extended research underway following phase 1/2 trial
The trial design did not include random assignment; instead, researchers compared guanabenz-treated patients with historical cases from the Vanishing White Matter Registry. Consequently, no untreated control group was enrolled concurrently. The authors emphasize that longer-term follow-up is necessary to verify the disease-modifying potential of the medication. It is important to note that guanabenz does not cure VWM, and it has not received regulatory approval as a treatment for this condition.
Follow-up studies at Amsterdam UMC are ongoing with children from the original cohort. These extensions will assess walking ability, neurological functions, brain imaging, safety profiles, and various doses of guanabenz over a longer duration. Currently, guanabenz remains available only within a research context for VWM. Originally developed to treat high blood pressure, it influences cellular stress pathways associated with the disease. The current data provide valuable clinical insights into the effects of this medication on children with early-onset vanishing white matter disease.