Key result
Treatment with ActRIIB:ALK4-Fc significantly improved systolic or diastolic function and corrected Ca2+ handling protein expression in murine models of cardiomyopathy.
Why the study?
Cardiomyopathies lack disease-modifying treatments, while dysregulated activin receptor signaling has been implicated in heart disease as a potential therapeutic target.
Does ActRIIB:ALK4-Fc improve systolic or diastolic function in murine models of cardiomyopathy induced by neuromuscular disease or diabetes mellitus?
Does ActRIIB:ALK4-Fc improve systolic or diastolic function in murine models of cardiomyopathy induced by neuromuscular disease or diabetes mellitus?
Inhibition of activin signaling using ActRIIB:ALK4-Fc improves cardiac function and corrects calcium handling protein expression in murine models of cardiomyopathy.
ActRIIB:ALK4-Fc improves murine cardiomyopathy; hypothesis-generating for human translation, no practice change.
Cardiomyopathies are ascribed to a variety of etiologies, present with diverse clinical phenotypes, and lack disease‐modifying treatments. Mounting evidence implicates dysregulated activin receptor signaling in heart disease and highlights inhibition of this pathway as a potential therapeutic target. Here, we explored the effects of activin ligand inhibition using ActRIIB:ALK4‐Fc, a heterodimeric receptor fusion protein, in two mechanistically distinct murine models of cardiomyopathy. Treatment with ActRIIB:ALK4‐Fc significantly improved systolic or diastolic function in cardiomyopathy induced by neuromuscular disease or diabetes mellitus. Moreover, ActRIIB:ALK4‐Fc corrected Ca2+ handling protein expression in diseased heart tissues, suggesting that activin signaling inhibition could alleviate cardiomyopathies in part by rebalancing aberrant intracellular Ca2+ homeostasis–a common underlying pathomechanism in diverse heart diseases.
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Li et al. (2022) studied Cardiomyopathy induced by neuromuscular disease and diabetes. ActRIIB:ALK4-Fc was evaluated on Systolic or diastolic function and Ca2+ handling protein expression. Treatment with ActRIIB:ALK4-Fc significantly improved systolic or diastolic function and corrected Ca2+ handling protein expression in murine models of cardiomyopathy.
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