AMSTERDAM, NETHERLANDS / RankWire.AI / – Researchers at Amsterdam UMC have found that guanabenz, an older drug used for blood pressure management, has the potential to delay vanishing white matter disease progression in pediatric patients. In a phase 1/2 trial, 33 ambulatory children were observed and their outcomes compared with 66 historical controls matched for demographic and clinical features. The study revealed that children treated with guanabenz had a markedly reduced risk of losing the ability to walk with support. Researchers published these findings in The Lancet Neurology in August 2026. Vanishing white matter disease, also known as VWM, is an uncommon inherited neurodegenerative disorder that frequently begins in early childhood.
The study included children with confirmed VWM diagnoses through genetic testing and magnetic resonance imaging. Eligibility criteria required disease onset at age six or younger and a maximum disease duration of eight years. Participants also needed 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 study. Their median age was 5.4 years, and the median treatment duration was 3.1 years.
The primary effectiveness measure centered on the loss of walking ability with support. Each treated child was matched with two untreated historical controls based on age at disease onset and disability level. The analysis yielded a hazard ratio of 0.33 for reaching the main walking endpoint, indicating a 67% lower hazard among those receiving guanabenz. Brain imaging supported these results, showing less white matter deterioration in treated children, with some exhibiting no detectable disease progression. The strongest treatment effects appeared in children whose disease started at age three or later.
Guanabenz lowers the risk of losing walking capacity
During safety assessments, 63 serious adverse events were reported among 25 of the 33 children. Investigators identified 30 of these as likely or very likely related to guanabenz. Among these, hallucinations accounted for 24 suspected unexpected serious adverse reactions affecting 18 children. These episodes mostly occurred during the first four months of treatment and typically resolved within months. Four cases involved severe constipation, and one involved transient low blood pressure with sedation; all required brief hospitalization and later improved.
Children started on oral guanabenz at a dose of 0.15 milligrams per kilogram of body weight daily. Researchers gradually increased doses over approximately six weeks to reach each child’s maximum tolerated dose, with an optimal target of 2 milligrams per kilogram daily. After four to six months, most children tolerated the medication well. No participants withdrew due to side effects, and no life-threatening events or deaths occurred among those receiving guanabenz.
Ongoing long-term monitoring after the clinical trial
The authors noted that the trial design did not involve random assignment of children to treatment or control groups. Instead, they compared treated patients with historical cases from the Vanishing White Matter Registry, which means there was no concurrent untreated control group. The researchers emphasized that a long-term extension study is needed to validate the potential disease-modifying effects. It is important to note that guanabenz does not cure VWM. 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 VWM treatment. Amsterdam UMC states that patients can only access the drug within a research context at this time. A follow-up study is underway to monitor long-term effects and evaluate different dosing regimens in children from the original trial. Researchers will assess walking ability, neurological function, brain imaging, safety outcomes, and other clinical parameters. These initial findings represent the first clinical evidence suggesting guanabenz can influence measurable disease progression in children with early-onset VWM, with longer-term research still in progress.