Preclinical Development of Cardioprotective microRNA Molecules (ProtectomiRs)

Summary

The aim of our work is to develop a new, innovative therapy to reduce the damage caused by myocardial infarction, thereby reducing mortality and the development of complicated heart failure. MicroRNAs constitute one group of small RNAs; a major advantage is that a single microRNA can influence the expression of a large number of target genes. This makes microRNA therapies particularly suitable for treating diseases with complex mechanisms, such as the damage caused by myocardial infarction. Our work consists of several phases. One goal is to identify new microRNAs that can reduce damage to the heart muscle. These heart-protective drug candidates are called ProtectomiRs. In further stages of our work, we will characterize these ProtectomiRs in detail and investigate their infarct-reducing effects in small animal models. ProtectomiR therapy could represent a breakthrough in the treatment of complex diseases such as oxygen deprivation-induced myocardial infarction and the subsequent heart failure. During the planned work, we will carry out the early phases of drug development, thereby providing numerous promising new drug candidate molecules for human clinical trials.

Participating leading researchers, collaboration partners, universities, companies

The project features key contributions from Dr. Györgyi Ferenc, a biochemist (Szeged, SZBK) and expert in small RNAs, and Dr. Péter Bencsik (University of Szeged, Department of Pharmacology), an expert in animal models of myocardial damage and cardioprotection.

Applied methods and tools

The research employs a series of experimental methods built upon one another in multiple steps. First, new ProtectomiR candidates will be selected based on previously obtained miRNA expression data. Their cytoprotective effects will then be examined in neonatal rat cardiomyocytes and the human AC16 cell line using a simulated ischemia-reperfusion model. The most promising molecules will be further tested at low dose ranges. Subsequently, at least three chemically modified variants will be pharmacokinetically and pharmacodynamically characterized in mice, including plasma and cardiac muscle expression, half-life, and regulation of target genes. Finally, the effects of the selected candidates will be evaluated in rat models of acute myocardial infarction and chronic heart failure.

Pictures

Gallery

3images

Mission and benefits

The mission of this research is to reduce post-infarction myocardial damage and the resulting development of heart failure through a novel microRNA-based approach. Its value lies in establishing a multi-target therapeutic direction that can bring us closer to more effective and personalized cardioprotective treatments.