Serine biosynthesis as a novel therapeutic target for dilated cardiomyopathy.
Isaac Perea-GilTimon SeegerArne A N BruyneelVittavat TermglinchanEmma MonteEsther W LimNirmal VadgamaTakaaki FurihataAlexandra A GavidiaJennifer Arthur AtaamNike BharuchaNoel Martinez-AmadorMohamed AmeenPooja NairRicardo SerranoBalpreet KaurDries A M FeyenSebastian DieckeMichael Paul SnyderChristian M MetalloMark MercolaIoannis KarakikesPublished in: European heart journal (2022)
A phenotypic screening platform using DCM iPSC-CMs was established for therapeutic target discovery. A combination of SMKIs ameliorated contractile and metabolic dysfunction in DCM iPSC-CMs mediated via the ATF4-dependent serine biosynthesis pathway. Together, these findings suggest that modulation of serine biosynthesis signalling may represent a novel genotype-agnostic therapeutic strategy for genetic DCM.