How to mend a broken heart?

How can a broken heart be repaired? Gene replacement therapy may work in some cases, say researchers from Japan

In a Stem Cell study published in January, researchers from Osaka University reported that heart cells from a patient with a hereditary heart disease called arrhythmogenic cardiomyopathy contracted incorrectly in the lab, which replaced the mutated gene responsible for repairing the defect.

Arrhythmogenic cardiomyopathy occurs due to mutations in genes associated with desmosomes, which form "welds" between cells that help them communicate and move in a coordinated fashion

"Previous studies in cardiomyocytes have shown that mutations in PKP2 play a pathological role in arrhythmic cardiomyopathy," said Hiroyuki Inoue, lead author of the study

To study how cells from a patient behaved in the lab, the researchers first took a blood sample from a young patient with arrhythmic cardiomyopathy, induced some of the blood cells to become stem cells, and then differentiated those stem cells into the heart cells

"Due to the lack of thrombophilin 2, cells with two mutated copies of PKP2 clearly showed reduced contractility and impaired desmosome assembly," explained senior author Shuichiro Higo

Replacing mutated PKP2 with an intact gene copy repaired defects in cell shrinkage and desmosome assembly, which the researchers could observe using time-lapse methods and fluorescently labeled desmosomes

"These findings demonstrate that our cardiomyocyte line recapitulates the pathology of arrhythmogenic cardiomyopathy and provides a fast and convenient platform for developing gene therapies for this disease," Higo said

Given that PKP2 is the most common gene associated with arrhythmic cardiomyopathy, and that PKP2 mutations can lead to severe disease, new treatments may help stop the disease from progressing

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Modeling reduced contractility and impaired desmosome assembly due to plakophilin-2 deficiency using isogenic iPS cell-derived cardiomyocytes