AKAP18-PLB interaction disruptors as treatment for myocardial infarction, phase 2

Heart attack is a common disease and is among the most common causes of death in the Western world, and is often treated with beta blockers as standard treatment. Beta blockers have a variety of side effects, because these drugs also affect a number of other organs besides the heart. In this project we want to test low molecular weight chemicals that alter protein-protein interactions in the protein complex AKAP18d-PLB-SERCA2 in cardiac myocytes as a treatment for myocardial infarction. The small molecule substances are optimized as pharmaceuticals and extensivly tested in cardiac muscle cells, also drug effect and no toxic effects have been documented. Through previous applications we have documented the pharmacokinetic properties of the small molecule substances and the terapautic effect of these molecules against ischemia-reperfusion injury in rats.
The purpose of the current project is to test this compound in pigs which have a similar cardiac response to myocardial infarction as humans, so we can be able to test these drugs in humans if the trial is positive. The current study will result in minimal to no distress for the animals, and if the test is positive this might lead to improved treatment for myocardial infarction. A maximal amount of 55 animals will be used in the study. The 3R priniciples will be conducted throughout the study, among other by multipple sampling from the same animal.