Gene Targeting Can Reverse Cardiac Fibrosis

The thickening and stiffening associated with cardiac fibrosis is an important indicator of heart failure, but could one gene loosen things up again? 

What is cardiac fibrosis? 

Fibrosis involves excess deposition of connective fibrous tissue and can be caused by scarring or undesirable proliferation of cardiac fibroblast cells – cells which specifically churn out connective tissue. This connective stuff is important for holding tissue together, but too much of it reduces elasticity and is a strong marker of heart failure risk. It’s therefore an important target for returning the heart to a more flexible, youthful state. 

One protein could change things

A protein called CCN5 encoded by one gene is found in the extracellular matrix – meaning the gel surrounding and encasing cells across the body. Researchers discovered that this particular protein is especially reduced in the hearts of patients with severe heart failure. They then decided to test it on a model of severe cardiac fibrosis to see whether it could have a beneficial effect. 

“Since CCN5 is a secreted protein, we may be able to deliver the CCN5 protein itself rather than the CCN5 gene in the form of recombinant virus or stem cells that are engineered to express CCN5. The efficacy of these alternative approaches has yet to be tested, but they certainly deserve a serious consideration,”

The left ventrice of a mouse heart. Credit Laurence Jackson, Centre for Advanced Biomedical Imaging, Wellcome Images

When they transferred the gene for CCN5 into heart tissue in an animal model they found that 8 weeks later fibrosis had actually been reversed. This means that transfer of either the gene via gene therapy, or direct delivery of the protein itself may actually be able to reverse symptoms – reducing heart failure risk and improving heart function. 

“Our research is the first to demonstrate the ability to reverse cardiac fibrosis in heart failure models by targeting a specific gene. These findings demonstrate that CCN5 may provide a novel platform for the development of targeted anti-cardiac fibrosis therapies, which could benefit many patients with previously untreatable heart failure” 

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