After acute myocardial infarction (AMI), the heart undergoes a process of pathological remodeling. One consequence is left ventricular systolic dysfunction, meaning that the left ventricle’s ability to pump blood is impaired. To compensate for this condition, the myocardium enlarges excessively and, as a result, becomes weaker. More than a decade ago, Professor Thomas Thum of Hannover Medical School in Germany discovered that a microRNA known as miR-132 is a key regulator of this harmful growth of cardiomyocytes, and that its marked accumulation is directly associated with pathological proliferation of cardiac muscle cells.
In 2016, Professor Thomas Thum founded Cardior and developed CDR132L, an inhibitor of miR-132. In 2024, the pharmaceutical giant Novo Nordisk acquired Cardior for more than €1 billion. In May 2026, researchers from Cardior Pharmaceuticals, a Novo Nordisk company, published a study in the leading international medical journal Nature Medicine titled “The microRNA inhibitor CDR132L in patients with reduced left ventricular ejection fraction after myocardial infarction: a randomized phase 2 trial.”
The paper reported data from a randomized phase 2 clinical trial of the miR-132 inhibitor CDR132L in patients with reduced left ventricular ejection fraction after myocardial infarction. The results showed that CDR132L was well tolerated, with no signs of liver, kidney, hematologic, or cardiac toxicity. Patients who already had severe adverse cardiac remodeling at the start of the trial appeared to benefit particularly from CDR132L treatment.
Despite major advances in pharmacological treatment, heart failure after myocardial infarction remains a leading cause of morbidity and mortality. Adverse left ventricular remodeling, characterized by ventricular dilation, hypertrophy, fibrosis, and systolic dysfunction, is the central pathophysiological process linking myocardial injury to progressive heart failure and death. Current drug therapies mainly target neurohormonal activation and hemodynamic load, but few interventions directly regulate the molecular and structural maladaptations of the myocardium. Therefore, therapeutic options that can effectively prevent or reverse post-infarction remodeling remain limited.
MicroRNAs, or miRNAs, are key post-transcriptional regulators in cardiovascular biology. Among them, miR-132 is upregulated during myocardial stress responses and acts as a critical driver of adverse remodeling. Sustained activation of miR-132 promotes cardiomyocyte hypertrophy, impaired calcium handling, reduced contractility, and myocardial fibrosis, all of which are hallmarks of the transition from compensatory injury to heart failure. In preclinical animal models, inhibition of miR-132 prevented and partially reversed pathological remodeling, thereby improving both systolic and diastolic function.
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CDR132L is a synthetic antisense oligonucleotide drug based on locked nucleic acid (LNA) technology, specifically designed and optimized to inhibit miR-132. In extensive preclinical studies, CDR132L demonstrated efficient myocardial uptake, dose-dependent inhibition of miR-132, and significant reversal of cardiac dysfunction in large-animal models of ischemic and non-ischemic heart failure. In a first-in-human phase 1b trial, CDR132L was well tolerated at doses up to 10 mg/kg, showed linear pharmacokinetics, achieved sustained target engagement, and produced a dose-dependent reduction in circulating miR-132.
On this basis, the research team conducted an international, multicenter, randomized, double-blind, placebo-controlled phase 2 clinical trial called HF-REVERT, designed to evaluate the efficacy and safety of CDR132L in patients with early left ventricular systolic dysfunction after acute myocardial infarction. The results showed that CDR132L was well tolerated, with no signals of liver, kidney, hematologic, or cardiac toxicity. The primary endpoint, the percentage change in left ventricular end-systolic volume index (LVESVI) at 6 months, improved in all groups, but there was no significant difference between the CDR132L treatment groups, at 5 mg/kg and 10 mg/kg, and the placebo group. Secondary endpoints, including left ventricular ejection fraction, global longitudinal strain, and N-terminal pro-B-type natriuretic peptide, also showed no significant differences between the CDR132L treatment groups and the placebo group.
Figure 1. Changes in LVESVI in patients treated after MI with placebo, CDR132L 5 mg kg-1 or CDR132L 10 mg kg-1. (Bauersachs J, et al., 2026)
Prespecified exploratory analyses suggested that CDR132L treatment may benefit patients whose hearts were already severely damaged before treatment, meaning patients with severe adverse cardiac remodeling. This supports the need for further evaluation of CDR132L, including in the setting of chronic heart failure.
Reference
- Bauersachs J, et al. The microRNA inhibitor CDR132L in patients with reduced left ventricular ejection fraction after myocardial infarction: a randomized phase 2 trial. Nature Medicine, 2026: 1-8.