AMSTERDAM, NETHERLANDS / RankWire.AI / – A study conducted by Amsterdam UMC indicates that guanabenz, an established medication for hypertension, might reduce the progression of vanishing white matter disease in pediatric patients. The phase 1/2 clinical trial involved 33 children who could walk and compared their outcomes with 66 historical controls matched for disease characteristics. Results showed that children receiving guanabenz had a notably reduced risk of losing the ability to walk with support. Researchers shared their findings in The Lancet Neurology in August 2026. Vanishing white matter disease, or VWM, is a rare inherited neurodegenerative disorder that frequently manifests in early childhood.
Participants in the trial had confirmed VWM diagnoses through genetic testing and magnetic resonance imaging. To be eligible, children needed to show disease onset at age six or younger and have a disease duration no longer than eight years. Additionally, they had to be able to walk at least ten steps with no more than light support from one hand. Between May 31, 2021, and May 31, 2024, researchers enrolled 33 eligible children, with 31 completing the study. Their median age was 5.4 years, and the median treatment duration reached 3.1 years.
The primary measure for assessing treatment effectiveness was the loss of walking with support. Each treated child was matched with two untreated historical controls based on disease onset and severity. The analysis revealed a hazard ratio of 0.33 for reaching the main walking endpoint, indicating a 67% lower estimated hazard in the treated group. Brain imaging further supported these findings, showing less white matter deterioration among treated children, with some exhibiting no detectable disease progression. The strongest effects were observed in children whose disease began at age three or later.
Guanabenz Demonstrates Potential to Decrease Risk of Losing Walking Ability
Throughout the trial, safety monitoring recorded 63 serious adverse events among 25 of the 33 children. Investigators assessed 30 of these events 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 generally resolved within months. Severe constipation was reported in three cases, and one participant experienced temporary low blood pressure with sedation. Each of these four events led to a brief hospital stay but eventually resolved.
Children began taking oral guanabenz at 0.15 milligrams per kilogram of body weight daily. The dose was gradually increased over approximately six weeks to reach each child’s maximum tolerated level. The study aimed for an optimal dose of 2 milligrams per kilogram daily. After the initial four to six months, researchers observed that children tolerated the medication well overall. No participant withdrew due to side effects, and no life-threatening events or deaths occurred during the trial among those receiving guanabenz.
Extended Follow-Up Is Ongoing to Assess Long-Term Effects Post-Trial
The researchers emphasized that the trial did not randomly assign children to treatment and control groups. Instead, they compared treated patients with historical cases from the Vanishing White Matter Registry. This approach meant the study lacked a concurrent untreated control group. The team indicated that a long-term extension study is necessary to confirm whether guanabenz can modify disease progression. It is important to note that guanabenz does not cure VWM. The disorder results from genetic mutations affecting eukaryotic initiation factor 2B, which controls the cellular integrated stress response targeted by the medication.
Currently, guanabenz is not approved by regulatory agencies for the treatment of vanishing white matter disease. According to Amsterdam UMC, patients can access the drug for VWM only within research settings at this time. Ongoing follow-up studies are monitoring long-term outcomes and exploring different guanabenz dosages in children from the original trial. These investigations will track walking ability, neurological function, brain imaging, safety, and other clinical measures. The new findings provide initial clinical evidence that guanabenz can influence measurable disease progression in eligible children with early-onset VWM, while longer-term research continues to develop.