Adrenoleukodystrophy (ALD)
https://www.sciencedirect.com/science/article/pii/S258953702500197X?via%3Dihub
Cerebral adrenoleukodystrophy (cALD) is a rare, genetic, and life-threatening brain disorder that can affect young boys. It causes damage to the brain’s white matter, leading to rapid neurological decline. The current treatment, haematopoietic stem cell transplantation (HSCT), can be effective but is high-risk, not widely available, and often delayed. While allogeneic (cells from a donor) and autologous modified (your own cells) HSCT are effective in some patients, the success is dependent on the time of transplant and the extent of cerebral disease. As a result, there is a critical need for safer, more accessible therapies. Leriglitazone is an oral drug designed to reduce inflammation, protect brain cells, and slow disease progression. In this ongoing clinical trial (NEXUS), boys aged 2–12 with early-stage cALD received daily leriglitazone for 24 weeks. The goal was to assess safety and early signs of benefit. Eleven boys were evaluated in this interim analysis and all remained clinically stable, and five (45%) showed no further disease activity on MRI scans. This suggests a possible halting of progression. Brain lesion growth slowed in all patients compared to the expected course of untreated disease. Blood tests also showed encouraging changes in key biomarkers of brain inflammation (MMP-9) and nerve damage (NfL), further supporting the drug’s potential benefit. Importantly, leriglitazone was well tolerated with no serious drug-related side effects. These early results suggest that leriglitazone could offer a safer alternative or complement to HSCT, especially for children who lack timely access to transplantation. While these findings are promising, longer-term follow-up and research is needed. The full 96-week trial will determine whether leriglitazone can provide lasting protection against this devastating disease.