AMSTERDAM, NETHERLANDS / RankWire.AI / – Researchers at Amsterdam UMC have reported that guanabenz, an older medication for blood pressure, could delay the progression of vanishing white matter disease in children. Their phase 1/2 trial involved 33 ambulatory children and compared their outcomes with 66 matched historical controls. The study revealed a notably reduced risk of losing the ability to walk with support among children treated with guanabenz. Researchers published these findings in The Lancet Neurology in August 2026. VWM, a rare inherited neurodegenerative disorder, often begins in early childhood and is characterized by progressive white matter loss.
The trial included children with confirmed VWM diagnosis through genetic testing and MRI scans. Eligible participants had disease onset at age six or younger and a disease duration of no more than eight years. They needed to be able to walk at least 10 steps with no more than light support from one hand. Between May 31, 2021, and May 31, 2024, 33 patients 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 measure of effectiveness focused on loss of walking ability with support. Each treated child was matched with two historical controls based on disease onset and severity. The hazard ratio for reaching the primary walking endpoint was 0.33, indicating a 67% reduction in risk for treated patients. Brain imaging supported these findings, showing less white matter deterioration, with some children exhibiting no progression. The strongest effects appeared in children whose disease started at age three or later.
Guanabenz Demonstrates Potential to Reduce Risk of Loss of Walking
Throughout safety monitoring, 63 serious adverse events were documented in 25 of the 33 children. Investigators considered 30 of these events as likely or very likely related to guanabenz. Notably, 18 children experienced hallucinations, which accounted for 24 suspected unexpected serious adverse reactions. These episodes mostly occurred within the first four months and generally subsided within months. Four children experienced severe constipation, and one had temporary low blood pressure with sedation; all events required brief hospitalization and eventually resolved.
Participants began with oral guanabenz at 0.15 milligrams per kilogram daily, with doses gradually increased over 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, children generally tolerated the treatment well; no one withdrew due to side effects, and no life-threatening events or deaths were reported among those receiving guanabenz.
Extended Follow-Up Continues Beyond the Clinical Trial
The researchers emphasized that the trial did not randomly assign children to treatment or control groups. Instead, they compared treated participants with historical cases from the Vanishing White Matter Registry, lacking a concurrent untreated group. They recommend a long-term extension study to verify the potential disease-modifying effects. It’s important to note that guanabenz does not cure VWM, which results from genetic defects affecting eukaryotic initiation factor 2B, a regulator of the cellular stress response targeted by the medication.
Guanabenz is not currently approved for VWM treatment. According to Amsterdam UMC, patients can only access it within research settings at this time. A follow-up study is ongoing, focusing on long-term monitoring and testing different doses in children from the original trial. The study will assess walking ability, neurological function, brain imaging, safety, and other clinical outcomes. These new findings offer initial clinical evidence that guanabenz can influence measurable disease progression in eligible children with early-onset VWM, with longer-term research still underway.