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Molecule identified that could counteract arrhythmogenic cardiomyopathy

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MB-3 is a synthetic, lab-created molecule used to limit the activity of the enzyme GCN5 which reduces the accumulation of fat in heart cells that characterize arrhythmogenic cardiomyopathy – a disease that has affected young sportsmen such as Livorno soccer player Piermario Morosini and Asiago field hockey player Darcy Robinson. The discovery by a team of biologists from Eurac Research comes after several years of research in collaboration with the Medical University of Innsbruck, the Monzino Cardiology Center and the University of Milan.

Arrhythmogenic cardiomyopathy is a genetic heart disease which affects one in 7,000 people. However, in some regions such as the northeast of Italy, the disease has been known to affect up to one person in 2,000. Classified as a rare disease, it is better known than other rare diseases due to its occasional yet alarming first symptom: sudden death. Even young athletes have been known to be affected by it. The hearts of those impacted become progressively suffocated by accumulations of fat and fibrous tissue resulting in varying degrees of debilitating forms of heart failure. In more severe cases this can even cause sudden and fatal malignant arrhythmias.
"At Eurac Research, we started working on arrhythmogenic cardiomyopathy in 2015, building on previous research by colleagues at the Monzino Cardiology Center in Milan," explains biologist Alessandra Rossini who leads the cardiovascular research group. "Thanks to a long series of experiments in our laboratories, we have studied what causes severe structural damage in the hearts of sick people in more and more detail. After several intermediate steps we have now come to understand that by using the molecule MB-3 to inhibit the enzyme GCN5, that is, to limit its activity, we can reduce the formation of fat accumulation in cells called cardiac fibroblasts. Now, further studies will be needed to understand whether this molecule works not only on isolated cells, but on patients with the disease."

Le macchie verdi sono accumuli di grasso che soffocano poco a poco le cellule del cuore dei malati di cardiomiopatia aritmogena. © Eurac Research | Marzia De Bortoli
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The paper

Full paper can be found in the J Cell Mol Med journal: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9258704/
Chiara Volani is the first author of this paper.

The study was funded in part by the International Cooperation Project (Joint Project) - South Tyrol- FWF (Italy-Austria), number 23623.

Related People

Alessandra Rossini

Marzia De Bortoli

Peter Pramstaller

Chiara Volani

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