Adrenoleukodystrophy (ALD)
https://www.cell.com/molecular-therapy-family/advances/fulltext/S3117-387X(26)00037-6
Cerebral adrenoleukodystrophy (CALD) is a serious, progressive condition that causes inflammation and damage to the brain’s white matter, which supports communication between nerve cells. It is associated with changes in the ABCD1 gene, leading to the accumulation of very long-chain fatty acids. Gene therapy aims to halt disease progression by correcting a patient’s blood stem cells so they can produce cells that support the body’s immune system. In this study, researchers investigated whether biomarkers in blood plasma and cerebrospinal fluid (CSF), the fluid surrounding the brain and spinal cord, could help monitor disease activity and treatment response. They assessed 20 potential biomarkers in boys with CALD before and for up to two years after gene therapy. The most promising findings involved two proteins associated with nervous system damage and inflammation: neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP). NfL, released into body fluids when nerve cells are damaged, showed a strong relationship with disease severity measured using magnetic resonance imaging (MRI). Two years after gene therapy, patients had a median 50% reduction in blood NfL levels. Importantly, NfL levels measured six months after treatment were associated with subsequent disease progression at 12 months. This suggests that NfL could help identify patients at greater risk of continued brain damage following treatment. These findings highlight the potential of blood-based biomarkers to complement MRI scans when monitoring CALD and assessing responses to gene therapy. Although further research is needed to validate these results in larger groups, NfL could eventually support earlier identification of patients who need closer monitoring, helping clinicians make more informed decisions about care.