Promising Oral Medication for Treating Fatal Childhood Brain Disease

A groundbreaking international research effort has identified a promising new oral drug that could significantly alter the treatment landscape for cerebral adrenoleukodystrophy (cALD), a rare and often fatal genetic disorder affecting young boys between the ages of 3 and 12. The investigational drug, leriglitazone, is currently being evaluated in the NEXUS trial, a multi-phase clinical study conducted across the United States, Europe, and South America. Recent analysis after six months involving 11 participants revealed that leriglitazone slowed the progression of disease symptoms in all patients, with nearly half of the boys showing no further signs of advancement—indicating a potential to halt the disease altogether. This early positive outcome suggests a breakthrough in treatment options for cALD, which until now has been limited to high-risk procedures like stem cell transplants and gene therapy, both carrying significant risks and accessibility issues.

Dr. Eric Mallack, the senior author of the study and Director of Clinical Research at the Moser Center for Leukodystrophies at Kennedy Krieger Institute, emphasized the significance of these findings. "This is the first indication that an oral medication could slow or stop this devastating disease," he stated. Dr. Mallack and his team contributed extensively to the study design, MRI assessments, and data analysis, leveraging years of expertise in MRI and disease natural history.

If approved, leriglitazone would become the first oral drug approved for cALD, potentially offering a safer and more accessible treatment for affected children. The study's results have been published in the journal eClinicalMedicine, marking a hopeful stride toward more effective management of this aggressive neurological disorder.

For more details, see the original publication: Ángeles García-Cazorla et al, "Safety and efficacy of leriglitazone in childhood cerebral adrenoleukodystrophy (NEXUS): an interim analysis of an open-label, phase 2/3 trial" in eClinicalMedicine (2025).