Serca Pharmaceuticals, a cardioprotection company that is developing 13-M, a novel first in class treatment for minimising tissue damage that occurs with blood reperfusion post myocardial infarction (MI) and stenting, has presented data on a novel approach to modulate the beta-adrenergic receptor-cAMP protein kinase A (PKA) signalling pathway that modulates the contractility.
The study aimed to find small molecular compounds that disrupt the AKAP18d-PLB protein to protein interaction which is specifically found in heart tissue, as this may protect from ischemia reperfusion injury in the treatment of acute myocardial infarction (heart attack).
13-M is a small NCE shown to have these important protein to protein interaction (PPI) characteristics with the capacity to modulate the SERCA2 Ca2+ pump. Targeting the AKAP18d-PLB interaction in this way, prevents the activation of SERCA2 and the Ca transport out of cytosol – and the contractile force and energy consumption upon adrenergic stress is reduced, without any effect on the patient’s heart rate.
MI is one of the leading causes of death and disability worldwide, affecting approximately seven million people each year. Without treatment, 30% of MI patients will go on to develop heart failure. Infarct size is the biggest predictor of post-MI heart failure and supported by over a decade of research in signalling pathways and SERCA2, 13-M has shown a 30% reduction in infarct size in preclinical models; in the clinic >10% infarct reduction is considered meaningful.
Kjetil Hestdal, Chief Executive Officer said: “These studies are an important step forward in the treatment of acute myocardial infarction and its consequences, and our findings presented at the HF 2023 conference, demonstrate that further development of 13-M as a highly promising cardioprotective therapy is warranted. We are excited by the progress we are making towards the development of a breakthrough new treatment for MI patients, that we expect to preserve heart tissue and function, a significant unmet need.”