Longevity & AgingBlocking a Single Enzyme Rescues Heart Cells From Chemotherapy Damage
Doxorubicin (DOX), a widely used chemotherapy drug, causes serious heart damage partly by disrupting NAD+ metabolism. This study reveals that DOX reprograms the kynurenine pathway (KP) — the primary route for de novo NAD+ synthesis from tryptophan — by upregulating the enzyme ACMSD while suppressing QPRT, diverting metabolites away from NAD+ production. Mice lacking IDO1, the pathway's initiating enzyme, suffered worse cardiac injury when given DOX. Pharmacological inhibition of ACMSD with the compound TES-1025 restored NAD+ levels, reduced oxidative stress, and improved cardiac function in DOX-treated mice. Crucially, TES-1025 did not interfere with DOX's ability to kill cancer cells, suggesting it could safely be co-administered during chemotherapy to protect the heart.
