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Targeting cardiac fibrosis with next generation RNA therapeutics

Project description

RNA therapeutics for prevention of heart failure

Heart failure (HF) is a deadly disease and the common cause of morbidity without relevant curative treatment. Cardiac fibrosis is the process of excessive collagenous scar tissue production by heart fibroblasts and is the main driver of HF development. The EU-funded FIBREX project aims to develop and bring to clinical readiness an innovative noncoding RNA (ncRNA)-based antisense oligonucleotide therapeutic product for the treatment of cardiac fibrosis-linked HF. The project is based on the discovery that imprinted long ncRNA gene maternally expressed 3 (MEG3) is the most promising target, expressed by cardiac fibroblasts and dysregulated in HF models.


The aim of FIBREX is developing a novel, highly innovative and close to clinical readiness noncoding RNA (ncRNA)-based antisense oligonucleotide therapeutic for the treatment of heart failure (HF) derived from cardiac fibrosis. HF is the most common cause of morbidity and mortality with pressing social and economic burden. HF remains a deadly disease with no curative treatment, underlining the need for innovative therapeutic strategies. The revolutionary technology we are proposing acts by reversing cardiac fibrosis, the main driver of HF development and progression. The excess fibrotic tissue leads to continous stiffening and impairment of the heart muscle. In our prior work, ncRNA Meg3 was identified as the most promising target, expressed mainly by cardiac fibroblasts and by consistent transcriptional dysregulation in HF models. The critical role for Meg3 in cardiac fibrogenesis was validated both in vitro and in vivo and a lead compound targeting Meg3 showed promising efficacy in relevant models, human tissues and excellent exploratory safety data. We propose a development project for an antiMEG3 inhibitor to reach close to clinical readiness, by completing non-clinical pharmacodynamic and safety studies.This work will be carried out by an experienced team headed by Prof. Thum, with a track record of discovering and licensing various ncRNA inhibitors programs, and creating a clinical stage spin-off company Cardior, reaching phase 2 development and Series B funding. We are confident that our technology with the requested support will be further advanced into an innovative novel drug candidate and, driven by the substantial value increase, the project will be transitioned into a spin-off drug development or a licensing-deal with the industry. The development of the unique, RNA-based antiMEG3 therapeutic approach for HF derived from excessive fibrosis offers a new opportunity to revolutionize medical practice, reduce health care costs and improve patient's life.


Net EU contribution
€ 2 499 482,00
Carl-Neuberg-Strasse 1
30625 Hannover

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Niedersachsen Hannover Region Hannover
Activity type
Higher or Secondary Education Establishments
Total cost
€ 2 499 482,00