Scientists in Japan have developed a credible heart
cell model for arrhythmogenic cardiomyopathy and observed a positive response
in the condition using PKP2 gene therapy.
Arrhythmogenic
cardiomyopathy (ACM) is an inherited heart muscle disorder that is thought to
affect one in 5,000 and can cause sudden cardiac arrest, particularly in
children and athletes. Previous studies have established that defects in the
PKP2 gene, which encodes the protein plakophilin-2, play a pathological role in
the condition but, until now, such research has only been carried out on cells
derived from healthy patients.
In this new study, researchers from Osaka
University successfully developed heart cells from patients with the condition
and observed that they fail to contract correctly when grown in the laboratory.
They observed that in replacing the mutated PKP2 gene responsible for this
effect, with an intact copy, this defect is fixed.
“The cells with two mutated
copies of PKP2 clearly exhibited reduced contractility and impaired desmosome
assembly due to plakophilin-2 deficiency,” explains Shuichiro Higo, senior
author. “These effects were also observed in cells with only one mutated copy
of PKP2, although they were less severe.”
Replacing the mutated PKP2
with an intact copy of the gene repaired the defects in both cell contraction
and desmosome assembly, which the researchers were able to observe using a
time-lapse approach and fluorescently labelled desmosomes.
“These findings suggest
that our cardiomyocyte cell lines recapitulate the pathology of arrhythmogenic
cardiomyopathy and provide a rapid and convenient platform for developing
gene-based therapies for this disease,” says Higo.
This study was published in
Stem Cell Reports.
European Journal of Case Reports and Clinical Images is an international open-access journal publi
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