KVAL: Novel cardioprotective drug candidate

Development of an anti-inflammatory drug for use in heart attacks. Myocardial infarction is one of the most prominent diseases within heart and vessel related disease. The main goal of this qualification project was to conduct an animal study to establish evidence that our new drug candidate (a peptide that counteracts inflammation) has a protective effect on the heart after infarction. Inflammation is a response to an infection or tissue damage triggered by the innate immune system, and plays a crucial role during myocardial infarction. Researchers from the Norwegian Center for Excellence in Molecular Inflammation Research (CEMIR) at NTNU have discovered a new drug candidate that inhibits the development of inflammation, and thus has the potential to reduce the damage to the heart caused by excessive inflammation after a heart attack. First, the drug candidate was thoroughly tested in human cells and in an ex vivo whole blood model with very promising results. Next, the drug candidate's ability to dampen inflammatory responses and improve survival and cardiac function in acute myocardial infarction was tested in a mouse model. Several anti-inflammatory cytokines were reduced after injection of the drug candidate in this model and this in accordance with a reduced size of the infarct in the group that received the drug candidate compared to the control group. The results from these studies provided quantitative information about the drug candidate's ability to reduce inflammation and improve the outcome of cardiac function in this murine acute myocardial infarction model. The results from the project open the way to continue the development of the candidate drug and accumulate data that can further arouse interest among relevant pharmaceutical players/licensees for further development.

CVDs inkludert MI er den ledende årsaken til sykelighet og dødelighet over hele verden. Til tross for potent farmakoterapi etter MI utvikler store deler av MI-pasienter hjertesvikt (HF) utløst av overdreven inflammatorisk respons. Betennelsesdrevet funksjonstap er et stort klinisk problem, noe som gjør betennelse til et viktig terapeutisk middel mål for å forbedre resultater etter MI. En rekke immunmodulerende midler har blitt testet i kliniske studier men ingen av tilnærmingene testet så langt resulterte i reell klinisk fordel for pasientene. Vi tror at vår kandidat kan gi en klinisk fordel da det ikke vil undertrykke immunsystemet som helhet, men er i stand til å dempe signalspor som forhindrer betennelsesdrevne komplikasjoner. Arbeidet med å videreutikle vår legemiddelkandidat som potensielt kan redusere forekomsten og alvorlighetsgraden av HF etter MI, og dermed redusere langsiktig sykelighet fortsetter. P7-Pen, til tross for at noen av endepunktmålingene i denne studien ikke kunne gjennomføres, representerer en mulighet til å være først i klassen for et kandidatlegemiddel som i fremtiden kan vise klinisk nytte for hjerteinfarktpasienter.