An international Phase 2 clinical trial led by MHH demonstrates the beneficial effects of the microRNA blocker in severely damaged hearts.
Aims to improve heart health after a heart attack using RNA-based therapy: Prof. Dr. Dr. Thomas Thum. Copyright: Karin Kaiser/MHH
Following an acute heart attack, pathological remodeling 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 and is thereby further weakened. The central 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 of Molecular and Translational Therapy Strategies at Hannover Medical School (MHH), has produced a synthetic antagonist called CDR132L that 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.
Now, the drug candidate CDR132L has been investigated in an international Phase 2 clinical trial involving patients who had recently suffered a heart attack and were experiencing heart failure. The HF-REVERT study showed that patients with already advanced cardiac remodeling at the start of the study could particularly benefit from treatment with CDR132L. The study results were presented on May 10, 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 controls pathological heart muscle growth
MicroRNA molecules belong to the so-called non-coding RNA (ncRNA) family, meaning they are not translated into specific proteins. Instead, they regulate a variety 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 primarily helps critically ill patients
The HF-REVERT study was conducted in seven European countries and the United Kingdom at approximately 80 study centers. A total of 294 patients were randomly assigned to three groups within three to 14 days of a heart attack. In addition to standard treatment for heart failure, they received either CDR132L in two different dosages 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 hematopoietic system, or the heart,” says Professor Thum. CDR132L was particularly effective in patients with already advanced cardiac remodeling, meaning their hearts were already severely damaged. “These observations support the further clinical development of the drug, particularly in the field of chronic heart failure,” emphasizes the cardiologist. The results represent an important step toward RNA-based therapies in cardiology. They offer great potential to positively influence disease progression 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 of Molecular and Translational Therapy Strategies. The MHH spin-off underscores the importance of university innovations for the development of new therapeutic approaches. Two additional clinical trials are currently underway in patients with chronic heart failure under the leadership of the Danish pharmaceutical company Novo Nordisk, which acquired the biopharmaceutical company Cardior in 2024.
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.
Text: Kirsten Pötzke