Heart failure (HF) is a widespread and burdensome condition characterized by pathological changes in the myocardium, resulting in pump failure and potential sudden death. Despite its prevalence, our understanding of the disease mechanisms remains limited, leading to a one-size-fits-all approach in HF therapy, which overlooks the various disease subtypes and individual differences.
In the Western world, the primary cause of HF is ischemic heart disease, often stemming from conditions like myocardial infarction (MI). To address this, a paradigm shift in HF research is required, focusing on groundbreaking concepts that can pave the way for an entirely new class of therapeutics targeting specific molecules and mechanisms within cardiomyocytes. Advances in cardiovascular biology have ushered in a gene-level approach to cardiac repair, known as gene therapy. Within this framework, non-coding RNAs (ncRNAs), including small ncRNAs (<200 nt, such as microRNAs) and long non-coding RNAs (lncRNAs; >200 nt), have emerged as potent regulators of cellular and tissue function at the post-transcriptional level. Notably, alterations in local ncRNA levels have been linked to disruptions in normal cellular processes and the development of conditions like cardiac remodeling and hypertrophy, highlighting their potential as therapeutic targets in HF patients.
The TRAIN-HEART program sought to broaden the scope of scientific inquiry and expedite the development of RNA-based therapeutics for the treatment of ischemic heart failure. MicroRNAs and long non-coding RNAs, in particular, play pivotal roles as regulators of cardiac tissue remodeling under chronic cardiac stress. Innovative therapies that target these RNA molecules hold significant promise in addressing the root causes of ischemic heart failure. Currently, aside from heart transplantation, no curative therapy exists for this debilitating disease. However, advancements in chemically modified oligonucleotides and drug delivery strategies are making substantial progress, addressing challenges related to delivery, specificity, and tolerability of RNA therapeutics.
