Cardiac fibrosis: safety assessment of a novel therapeutic approach

Approximately four million people in Germany suffer from heart failure. A key pathophysiological component of this condition is cardiac fibrosis, which contributes to the progressive deterioration of heart function. Researchers at Hannover Medical School identified the long non-coding RNA (lncRNA) Meg3 as a promising therapeutic target for fibrotic changes in heart failure. Inhibition of lncRNA Meg3 using a specific inhibitor (AntiMEG3) led to a significant reduction in cardiac fibrosis in a mouse model.

As part of the EU-funded FIBREX project, which aims to advance this inhibitor towards a drug candidate, regulatory safety studies on the AntiMEG3 inhibitor were conducted at Fraunhofer ITEM. These included pharmacokinetic analyses, safety pharmacology assessments for the heart and lungs, a genotoxicity test, and a toxicological dose-range finding study. The objective was to evaluate the undesirable and adverse effects of the AntiMEG3 inhibitor following intravenous administration in rats and to characterize its toxic potential based on clinical observations, hematology, immunotoxicity and histopathology. Under the study conditions, ITEM researchers were able to determine a No Observed Adverse Effect Level (NOAEL).