Peroxisome Biogenesis Disorder (PBD)
https://www.nature.com/articles/s41551-026-01651-5
Zellweger spectrum disorder (ZSD) is a rare inherited condition caused by changes in genes that help cells build peroxisomes. Peroxisomes play an essential role in breaking down certain fats and removing harmful substances from the body. When they do not work properly, toxic substances build up, causing damage to multiple organs, particularly the liver and brain. Current treatments mainly focus on managing symptoms and cannot correct the underlying genetic cause. In this study, researchers investigated whether a gene-editing technique called base editing could repair one of the most common disease-causing changes in the PEX1 gene, which affects around 30% of people with ZSD. Using a mouse model of the disease, they delivered the editing tool directly to the liver, where it corrected up to 60% of the faulty genes. The treatment restored peroxisome function, reduced the build-up of harmful fats and toxic bile acid compounds, improved liver health, and helped the mice gain weight. Similar benefits were seen when the editing tool was delivered using either a viral vector or a non-viral lipid nanoparticle system, although the latter produced lower levels of gene correction. The researchers also tested the approach in cells donated by people with ZSD, where more than 80% of the faulty PEX1 genes were successfully corrected, restoring normal peroxisome activity. Importantly, the treatment caused very few unintended genetic changes. Although these findings are still at the preclinical stage, they provide encouraging evidence that base editing could one day become a treatment that targets the root cause of ZSD, offering hope for people and families affected by this devastating condition.