Lab-cultured heart tissues derived from patients’ stem cells are a suitable model to study the progression of Friedreich’s ataxia (FA) and to develop and test new therapies, a study says.
The study, “Correlation between frataxin expression and contractility revealed by in vitro Friedreich’s ataxia cardiac tissue models engineered from human pluripotent stem cells,” was published in Stem Cell Research & Therapy.
FA is a rare, genetic, progressive disorder that affects the nerves and muscles. The disease is caused by the repetition of three nucleotides — the building blocks of DNA — specifically, one guanine (G) and two adenines (A) in the first intron of the FXN gene. An intron is a region of the gene that does not encode for a protein.
This leads to a significant decrease in levels of frataxin, a protein involved in iron metabolism that is encoded by the FXN gene. That deficiency, in turn, leads to the accumulation of iron deposits inside cells of the heart and brain, compromising their normal function.
As a result, many FA patients develop heart disease that may progress to heart failure, the leading cause of death among people with the disorder.
“[Mouse] models have been developed to study disease [development] in the past two decades; however, differences between human and mouse physiology and metabolism have limited the relevance of animal studies in cardiac disease conditions,” the researchers said.
In this study, a group of investigators from Novoheart, a biotech company focused on the use of stem cells for therapeutic purposes, and their collaborators set out to develop an in vitro model of FA that fully mimicked the effects the disorder has on a patient’s heart in an attempt to overcome the limitations posed by the use of animal models.
They first created heart cells (ventricular cardiomyocytes) derived from induced pluripotent stem cells — cells that are able to grow into any type of cell — obtained from healthy individuals and FA patients.