In a study published in the journal Science Translational Medicine, researchers from Osaka University showed that a previously unknown mutation can lead to a condition called dilated cardiomyopathy, which is one of the main causes of heart failure.

The human heart, the size of a fist, located just behind and slightly left of the breastbone, tirelessly beats an average of 100,000 times a day. However, conditions that stop the heart from pumping blood efficiently can cause serious problems and ultimately require heart transplantation.

Heart failure refers to an incurable condition where the heart is no longer able to meet the body's demands in terms of blood supply. It is one of the most common causes of death and it affects almost 40 million people worldwide, representing a huge public health problem. One of the main factors leading to heart failure is a disease called dilated cardiomyopathy (or DCM). DCM is characterised by dilation of the heart's chambers and a pumping disfunction. Previous research has shown that DCM is often inherited and has a genetic basis.

However, for up to 80 per cent of the familial DCM cases, the genetic mutation causing the disease has still not been known.
The research team identified a gene called BAG5 as a novel causative gene for DCM. First, they studied patients from different families, highlighting a correlation between loss of function mutations in the BAG5 gene and DCM.

The researchers found that this mutation has a complete penetrance, meaning that 100 per cent of the individuals presenting it will develop the disease. They then found in an experimental model of dilated cardiomyopathy that without BAG5 exhibited the same symptoms of human DCM, such as dilatation of the heart's chambers and irregular heart rhythm. This indicated that mutations that erase the function of BAG5 can cause cardiomyopathy.

AAV gene therapy refers to an innovative form of therapy aimed at fixing mutated genes in diseases that have a genetic cause like DCM. Therefore, these findings have paved the way for a potential precision medicine treatment based on gene therapy.