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FORNY20-FORNY2020

KVAL: Novel cardioprotective drug candidate

Alternative title: Development of a novel anti-inflammatory drug with potential protective impact on acute myocardial infarction (MI).

Awarded: NOK 0.50 mill.

Development of anti-inflammatory drug for use in myocardial infarction. Myocardial infarction is one of the most prominent diseases in cardiovascular related disease. The main goal of this qualification project is to conduct an animal study to establish evidence that our new candidate drug has a protective effect on the heart after a heart attack. We want to test whether: 1) the drug candidate reduces inflammation via attenuation of the level of inflammatory factors in the blood after induced myocardial infarction, and 2) whether the drug candidate improves the survival rate and heart functions. Inflammation is a response to an infection or tissue damage triggered by the innate immune system, and plays a crucial role during a heart attack (MI). Researchers from the Norwegian Center for Outstanding Molecular Inflammation Research (CEMIR) at NTNU have discovered a new drug candidate that inhibits the development of inflammation, and which thus has a potential to reduce the damage to the heart caused by excessive inflammation after MI. The effect of the drug candidate has been thoroughly tested in human cells and in an ex vivo whole blood model with very promising results. This project will, if we succeed, provide evidence of the concept that our drug candidate is able to curb inflammatory responses and improve survival and cardiac function in acute myocardial infarction. The study will also provide quantitative information on the drug's ability to reduce inflammation. A successful outcome of the project will open up for more comprehensive testing of the candidate drug in other models of MI and attract the interest of potential major pharmaceutical players / licensees for further development.

Inflammation, a response to infection or injury triggered by the innate immune system, plays a crucial role in myocardial infarction (MI), one of the most prominent diseases within cardiovascular disease (CVD). Researchers from the Norwegian Centre of Excellence in Molecular Inflammation Research (CEMIR) at NTNU have discovered a new drug candidate, SLAMF1 derived peptide, which inhibits TLRs-mediated inflammatory response, and thereby has a potential to reduce the damage of the heart caused by excessive inflammation following MI. The drug candidate precisely targets the innate immune system and interferes with pro-inflammatory cytokines expression in response to the ligation of both TLR4 and TLR9. The safety and efficacy of the peptides to regulate the cytokine production were thoroughly tested in primary human monocytes, THP-1 cell line and an ex vivo whole blood model with very promising results. In this project we will provide a proof of concept that our drug candidate is able to suppress inflammatory responses induced by acute MI and improve survival and heart function after acute MI. The study will provide quantitative measures of the drug’s ability to reduce inflammation by providing numerical readouts for the level of inhibition of cytokines in plasma. It will also provide survival rates and evaluation of heart functions for the survived animals treated with control or active peptides. The successful outcome will open for more extensive testing of the drug candidate in other models of MI and to attract the interest and initiate a dialogue with potential licensees.

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FORNY20-FORNY2020