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An international Phase 2 clinical trial led by MHH demonstrates the beneficial effects of the microRNA blocker in severely damaged hearts.
Following an acute heart attack, pathological remodelling processes occur in the heart. One consequence is so-called left ventricular systolic dysfunction, in which the pumping function of the left ventricle is impaired. To compensate for this, the heart muscle enlarges excessively, thereby becoming further weakened. The key regulator of this harmful growth of heart muscle cells is microRNA-132 (miR-132). A team led by Prof. Dr Dr Thomas Thum, Director of the Institute for Molecular and Translational Therapeutic Strategies at Hannover Medical School (MHH), has produced a synthetic antagonist called CDR132L, which can block the main switch for cardiac hypertrophy and reverse chronic heart failure. The researchers have already demonstrated this in animal models and early clinical trials.
The drug candidate CDR132L has now been investigated in an international Phase 2 clinical trial involving patients who have recently suffered a heart attack and have heart failure. The HF-REVERT study has shown that patients with already advanced cardiac remodelling at the start of the study could benefit particularly from treatment with CDR132L. The results of the study were presented on 10 May 2026 at the Heart Failure Association (HFA) Congress of the European Society of Cardiology in Barcelona and published simultaneously in the journal ‘Nature Medicine’.
MicroRNA regulates pathological heart muscle growth
MicroRNA molecules belong to a class of molecules known as non-coding RNA (ncRNA), meaning they are not translated into specific proteins. Instead, they regulate a wide range of cellular processes – such as how a cell grows, whether it divides, or what type of cell it develops into. On the other hand, excessive microRNA activity can alter gene regulation and thereby trigger diseases. One example of this is miR-132. More than ten years ago, Professor Thum’s research team discovered that a massive accumulation of this microRNA is directly linked to the pathological proliferation of heart muscle cells. The antisense oligonucleotide blocker CDR132L is the first ncRNA-based therapy to be used in Phase II trials for heart disease.
CDR132L is particularly beneficial for seriously ill patients
The HF-REVERT trial was conducted at around 80 study centres across seven European countries and the United Kingdom. A total of 294 patients were randomly assigned to three groups within three to 14 days of suffering a heart attack. In addition to standard treatment for heart failure, they received either CDR132L in two different doses or a placebo, administered in three intravenous doses at four-week intervals. The analysis was based on 280 patients who had received at least one dose. “Our study has demonstrated that CDR132L is safe and well-tolerated and does not cause any harmful side effects on the liver, kidneys, the haematopoietic system or the heart,” says Professor Thum. CDR132L was particularly effective in patients with already advanced cardiac remodelling, meaning their hearts were already severely damaged. “These findings support the further clinical development of the drug, particularly in the field of chronic heart failure,” emphasises the cardiologist. The results represent an important step towards RNA-based therapies in cardiology. They offer great potential for positively influencing the progression of the disease in patients with heart failure.
CDR132L was developed by Cardior Pharmaceuticals GmbH, which was founded in 2016 by Prof. Dr Dr Thomas Thum and is based on his research at the Institute for Molecular and Translational Therapy Strategies. This MHH spin-off highlights the importance of university-based innovation for the development of new therapeutic approaches. Two further clinical trials are currently underway in patients with chronic heart failure, led by the Danish pharmaceutical group Novo Nordisk, which acquired the biopharmaceutical company Cardior in 2024.
SERVICE:
Further information is available from Prof. Dr Dr Thomas Thum, thum.thomas@mh-hannover.de.
The original paper “The microRNA inhibitor CDR132L in patients with reduced left ventricular ejection fraction after myocardial infarction: a randomized phase 2 trial” can be found here: https://www.nature.com/articles/s41591-026-04408-4
Aims to improve heart health after a heart attack using RNA-based therapy: Prof. Dr Dr Thomas Thum.
Copyright: Karin Kaiser/MHH
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