There is a rare inherited heart condition that affects athletes and has no treatment to stall its progression. But researchers are a step closer to developing therapies for the deadly condition, known as arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C).
In a paper published on Sunday in Nature, scientists at Sanford-Burnham Medical Research Institute and Johns Hopkins University report how they used skin cells from ARVD/C patients to recreate the adult-onset disease in a laboratory dish - the first maturation-based "disease in a dish" model for the condition.
Heart muscle cells were generated from ARVD/C patients' own skin cells using new stem cell-based technology created by 2012 Nobel Prize winner Dr Shinya Yamanaka.
However, most of these heart cells were immature, and so were no use for studying the disease or testing new therapeutic drugs. The researchers had to find a way to induce signs of the adult disease in the embryonic-like cells.
After nearly a year of trial and error, the scientists finally figured it out: they made the cells' metabolism more like that found in adult hearts. They applied several cocktails to the model to trigger the shift to adult metabolism, which uses fat rather than sugar for energy production. This led to the discovery that metabolic malfunction is at the core of ARVD/C disease.
The team also tracked down the final piece of the puzzle to make patient-specific heart muscle cells behave like sick ARVD/C hearts: the abnormal over-activation of a protein called PPARg.
In the course of developing this "disease in a dish" model, the researchers also presented new potential targets for treating the heart condition. Previously, scientists had attributed ARVD/C to weakened connections between heart muscle cells, which occur only in half of the patients.
Dr Vincent Chen Huei-sheng, associate professor at Sanford-Burnham, was the senior author of the study.
His team was recently awarded a grant from the California Institute for Regenerative Medicine to create additional ARVD/C models to determine whether all patients develop the disease via the same metabolic defects discovered in this study.