Development of a Mechanism-Based Next-Generation Therapeutic for Heart Failure Derived From the Dark Genome

The ability of nucleic acids for intramolecular interactions opens manifold opportunities for novel medicines that have the potential to treat intractable human disorders, including heart disease. In this context, microRNAs have been identified as pleiotropic regulators of disease pathways and consequently as powerful therapeutic targets. With antisense oligonucleotides novel drug modalities are available to specifically inhibit as well as correct derailed microRNAs including pathological downstream pathways potentially restoring hallmarks of disease. However, only a handful of microRNA-targeting drugs underwent clinical testing so far, and none in the cardiovascular field. In this paper, the authors introduce the first-ever microRNA-based therapy that entered clinical trials in heart disease and present the previous development from target identification to first-in-human studies.