AMSTERDAM, NETHERLANDS / RankWire.AI / – The findings suggest that guanabenz, an older medication used to manage blood pressure, may help decelerate the decline of white matter in children affected by vanishing white matter disease, or VWM. This promising outcome emerged from a phase 1/2 trial involving 33 ambulatory children, which compared their progression to that of 66 matched historical controls. The study demonstrated a significantly reduced risk of losing the ability to walk with support among children treated with guanabenz. Researchers published their results in The Lancet Neurology in August 2026. VWM is a rare inherited neurodegenerative disorder that commonly begins in early childhood.
Participants in the trial were children with confirmed VWM diagnoses through genetic testing and magnetic resonance imaging. Eligibility criteria included disease onset at age six or younger and a maximum disease duration of eight years. They 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 measure of effectiveness was the loss of walking ability with support. Each treated child was matched with two historical controls based on disease onset and level of disability. The analysis yielded 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 revealed less white matter deterioration in treated children, some of whom showed no detectable progression. The strongest treatment effect was observed in children whose disease started at age three or later.
Guanabenz appears to lower the risk of losing walking capacity
Throughout the trial, 63 serious adverse events were recorded among 25 of the 33 children. Investigators judged 30 of these events as likely or very likely related to guanabenz. Notably, 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 of onset. Four cases involved severe constipation, while another involved temporary low blood pressure with sedation. All four events required brief hospital stays and eventually resolved.
Participants began treatment with oral guanabenz at 0.15 milligrams per kilogram of body weight daily. Doses were gradually increased over about six weeks to each child’s maximum tolerated level, with an optimal target dose set at 2 milligrams per kilogram daily. After the initial four to six months, researchers reported that most children tolerated the medication well. No participant withdrew due to side effects, and no life-threatening events or deaths occurred among those receiving guanabenz.
Ongoing long-term assessment following the clinical trial
The researchers emphasized that the study lacked randomization, as children were not assigned randomly to treatment or control groups. Instead, they compared treated participants with historical patients from the Vanishing White Matter Registry, meaning there was no concurrent untreated control group. The team stated that a long-term extension study is necessary to confirm the potential disease-modifying effects. It is important to note that guanabenz does not cure VWM; the condition results from genetic defects affecting eukaryotic initiation factor 2B, which regulates the cellular integrated stress response targeted by the drug.
Currently, guanabenz is not approved by regulatory agencies for the treatment of vanishing white matter disease. Amsterdam UMC states that patients can access the medication for VWM only within research settings. A longer-term follow-up study is ongoing, assessing different doses of guanabenz in children from the original trial. Researchers will monitor walking ability, neurological function, brain imaging, safety, and other clinical markers. These initial findings provide the first clinical evidence that guanabenz may influence measurable disease progression in children with early-onset VWM, while further research continues to evaluate its long-term effects.