Scarring of heart tissue can be slowed but not stopped, and can lead to heart failure. But a new study has shown that an existing immunotherapy could stop scar tissue formation after heart attacks.
When the heart sustains an injury, such as a heart attack, the damaged tissue often scars over. In the short term, it helps this vital organ maintain its structure, but the problem is this tissue doesn’t beat. That throws off the rhythm of contractions and can eventually lead to heart failure, which is fatal without drastic intervention like a transplant.
“After scar tissue forms in the heart, its ability to recover is dramatically impaired or impossible,” said Kory Lavine, senior author of the study. “Current treatments can help relieve symptoms and slow the progression, but there is a tremendous need for better therapies that actually stop the disease process and prevent the formation of new scar tissue that causes a loss of heart function. We are hopeful our study will lead to clinical trials investigating this immunotherapy strategy in heart failure patients.”
Fibroblasts are cells that help grow new connective tissue, and in the heart there are multiple types. Some can grow new tissue that beats, which is obviously important for repairing damage after a heart attack. Others grow static scar tissue instead, which ends up being more harmful. Identifying which populations are which is the tricky part, but with new advanced single cell sequencing technologies, the researchers on the new study were able to do just that.
First, the team studied gene expression in 45 donated human hearts, including some that were healthy, some that were damaged by prior heart attacks and others that were chronically failing. From this, they discovered that a population called FAP+ fibroblasts contribute to the formation of scar tissue but not healthy, beating tissue.
Next, they set out to investigate whether these cells could be blocked. A signaling molecule called IL-1 beta was found to be key to the process of creating scar tissue in the heart. The researchers tested a monoclonal antibody that blocks IL-1 beta, and sure enough, treated mice showed fewer FAP+ fibroblasts, less scarring and better cardiac function.
Importantly, there are two monoclonal antibodies that are already approved by the FDA which can block IL-1 signaling. While these are currently used to treat inflammatory disorders, one was evaluated as a treatment for atherosclerosis – and may have incidentally provided evidence to back up its use in reducing heart scarring.
“Even though this trial was not designed to test this treatment in heart failure, there are hints in the data that the monoclonal antibody might be beneficial for patients with heart failure,” said Lavine. “Secondary analyses of the data from this trial showed that the treatment was associated with a sizable reduction in heart failure admissions compared with standard care. Our new study may help explain why.”
This means that it might not be too long before this kind of immunotherapy can be used clinically to break the chain between heart attacks and heart failure. However, more work will need to be done to reduce other side effects, including an apparently increased risk of infection.
The research was published in the journal Nature.
