Australian researchers have successfully turned stem cells from Friedreich’s ataxia (FA) patients into heart cells to study molecular anomalies that may contribute to this disease.
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These “heart cells in a dish” provide valuable information for the design of novel treatments.
Their study, “Friedreich’s ataxia induced pluripotent stem cell-derived cardiomyocytes display electrophysiological abnormalities and calcium handling deficiency.” appeared in the journal Aging.
FA is caused by low levels of the frataxin protein due to anomalies in the gene sequence encoding this protein — repeats of DNA portions within the gene. The higher the number of repeats, the sooner the onset of FA and its associated complications.
Frataxin plays an important role in the mitochondria, the cell’s powerhouse, so the mutated protein accounts for several symptoms that reflect deficiencies in energy production. The heart is one of the organs affected by this lack of energy.
“Cardiomyopathy is detected in two-thirds of individuals with FRDA [Friedreich’s ataxia],” researchers wrote. “Individuals with FRDA generally present with progressive cardiomyopathy of the left ventricle, which is the leading cause of death in FRDA due to arrhythmias and/or heart failure.”
Previous studies have shown that death of heart cells, or cardiomyocytes, and fibrosis may contribute to heart complications in FA, but little is known about the disease’s impact on the heart.
Researchers generated stem cell cultures using cells from three FA patients with heart complications. They then stimulated the development of these stem cells into cardiomyocytes — basically, heart cells in a dish.
The new cardiomyocytes had low levels of frataxin, as expected, but also abnormal ionic currents, which are crucial for the normal functioning of these cells. They also had more variation in their beating rates, which was linked to deficient calcium control, ultimately affecting how the cardiomyocytes work.
Together, these results pave the way for understanding how FA patients develop abnormal heart activity — as well as the use of induced stem cells to study cardiomyopathy within the context of this disease.
“Importantly, our data clearly indicates that FRDA iPSC [stem cells]- derived cardiomyocytes can be used for screening of compounds able to alter or reverse phenotypes, in human cells, hence providing a novel and unique tool for FRDA research,” researchers concluded.