Anyone who carries it will develop the disease 100%, warns researchers.
Heart failure is an incurable illness in which the heart is unable to meet the body’s blood supply demands. It is one of the leading causes of death, affecting about 40 million people worldwide and posing a major public health issue.
A condition known as dilated cardiomyopathy is one of the main causes of heart failure (or DCM). DCM is characterized by heart chamber dilatation and pumping dysfunction.
DCM is typically hereditary and has a genetic foundation, according to earlier studies. However, for up to 80% of familial DCM cases, the genetic mutation causing the disease is still unknown.
In this study, the researchers discovered BAG5 as a novel DCM causal gene. First, they looked at patients from various families, finding a link between BAG5 gene loss of function mutations and DCM.
Further, they noted that this mutation is completely penetrant, indicating that 100% of those who carry it will develop the disease.
Their research on mice with DCM showed that mice lacking BAG5 had the same symptoms as humans, like dilated heart chambers and irregular heart rhythm.
This suggests that mutations that disable BAG5’s function can result in cardiomyopathy.
“Here we showed that loss of BAG5 perturbs calcium handling in mouse cardiomyocytes,” said Dr. Hideyuki Hakui, lead author of the study.
BAG5 is required for calcium handling in heart muscle cells, and calcium is required for a regular rhythm and overall cardiac muscle health, which explains why BAG5 deficiency causes cardiomyopathy.
“After demonstrating that BAG5 mutations led to loss of functional BAG5 protein,” added Dr. Yoshihiro Asano, senior author of the study, “we also showed that administration of an AAV9-BAG5 vector in a murine model could restore cardiac function. This finding suggests that gene therapy with adeno-associated viruses (AAV) should be further investigated as a possible treatment alternative to heart transplantation for patients who are BAG5 deficient.”
AAV gene therapy is a novel type of treatment targeted at correcting faulty genes in diseases with a hereditary etiology, such as DCM. As a result, these findings pave the path for a future gene therapy-based precision medicine treatment.
Source: 10.1126/scitranslmed.abf3274
Image Credit: Getty
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