In the study, researchers from Osaka University showed that a previously unknown mutation can lead to a condition called dilated cardiomyopathy, one of the main causes of heart failure. heart.
Heart failure is an incurable condition where the heart is no longer able to meet the body’s needs for blood supply. It is one of the most common causes of death and it affects nearly 40 million people worldwide, posing a huge public health problem.
One of the main factors leading to heart failure is a condition known as dilated cardiomyopathy (or DCM). DCM is characterized by dilation of the cardiac chambers and pump dysfunction. Previous research has shown that DCM is often inherited and has a genetic basis.
However, in up to 80% of familial DCM cases, we still don’t know the genetic mutation that causes the disease.
The team identified a gene called BAG5 as a novel pathogenic gene for DCM. They first studied patients from different families, highlighting the correlation between loss-of-function mutations in the BAG5 and DCM genes.
The researchers found that the mutation is fully penetrative, meaning that 100 percent of individuals with expression of it will develop the disease.
They then found in a mouse model of dilated cardiomyopathy that mice without BAG5 had the same symptoms of human DCM, such as dilated heart chambers and irregular heartbeat. This indicates that deletion mutants of BAG5 can induce cardiomyopathy.
Dr Hideyuki Hakui, lead author of the study, said: “Here, we have shown that loss of BAG5 affects calcium processing in mouse cardiomyocytes. BAG5 is important for the processing of calcium in cardiomyocytes, and calcium is needed for regular rhythm and overall heart muscle health, explaining why loss of BAG5 leads to cardiomyopathy.
Dr Yoshihiro Asano, senior author of the study continued: “After demonstrating that BAG5 mutations lead to loss of the functional BAG5 protein, we also showed that using the AAV9-BAG5 vector in the model Rats can restore heart function. This finding suggests that gene therapy with adeno-associated viruses (AAVs) should be further investigated as a possible alternative to heart transplantation for BAG5-deficient patients. ”
AAV gene therapy is an innovative form of therapy aimed at correcting mutated genes in diseases with genetic causes such as DCM. These findings thus pave the way for a potential precision medicine treatment based on gene therapy.