For his investigations, the scientist and his team first took blood cells (peripheral blood mononuclear cells) from patients suffering from a genetic variant of HCM and converted them into induced pluripotent stem cells. In these patients, the MYBPC3 gene is mutated. The mutation was then genetically eliminated in the cells using the CRISPR/Cas9 method. The researchers then developed the cells into heart muscle cells and compared their properties with those of healthy heart muscle cells.

The scientists found out that the clinical picture of HCM was not caused by a protein deficiency, as earlier supposed, but by a molecular stress response of the heart muscle cells, which leads to the typical symptoms of hypertrophic hypcardiomyopathy via reaction steps that are not yet known.

Once again, this type of research has shown that it enables fundamental research, which is important for a development of effective drugs.

The team has published their work in the journal Circulation.
Seeger, T. et al. (2019). A premature termination Codon mutation in MYBPC3 Causes Hypertrophic cardiomyopathy via Chronic Activation of Nonsense-Mediated Decay. Circulation 139: 799-811.

Source:
https://www.klinikum.uni-heidelberg.de/newsroom/winterstein-preis-fur-den-heidelberger-herzforscher-dr-timon-seeger/