Overview

• SickKids researchers used a genetic suppression screen to identify ABHD18 as a regulator of cardiolipin metabolism that modifies the effects of TAFAZZIN deficiency.
• The small‑molecule inhibitor ABD646 lowered monolysocardiolipin in patient‑derived cells and a zebrafish model, with observed improvements in cardiac metrics.
• Mechanistic data indicate ABHD18 converts cardiolipin to MLCL in vitro, and its inactivation in cells and mice shifts lipid profiles toward native cardiolipin.
• Barth syndrome is an X‑linked mitochondrial disorder affecting roughly 500 people worldwide, primarily males, with limited treatment options.
• The findings, published in Nature, establish a disease‑modifying target in preclinical models, with further development needed before any human therapy.