Genetic Background Influences Nicotinamide Riboside Response in Barth Syndrome: Preclinical Findings

Synopsis

Barth Syndrome is a rare genetic disorder caused by mutations in the TAFAZZIN (TAZ) gene, which affects mitochondrial function by disrupting cardiolipin remodeling. While clinical trials are promising, there is currently no cure. Because the same TAZ mutation can cause different symptoms in different patients, traditional animal or cell models cannot fully capture human disease variability. To address this, researchers created a panel of 10 fruit fly (Drosophila) lines, each carrying the same TAZ mutation but in different genetic backgrounds, to better reflect natural variation. As a test case, they treated these flies with nicotinamide riboside (NR), a therapy with known benefits, and found that responses varied across genetic backgrounds. This panel provides a valuable tool for pre-clinical testing of emerging therapies for Barth Syndrome.

Journal

PLOS ONE