Immunotherapy may be an effective treatment strategy for heart failure

A new study from Washington University School of Medicine in St. Louis shows that some immunotherapy – Similar to those approved by the Food and Drug Administration (FDA) to treat inflammatory conditions such as arthritis. It may also be an effective treatment strategy for heart failure.

The study will be published in the journal Oct. 23. nature.

After a heart attack, viral infection, or other heart damage, scar tissue often forms in the heart muscle, where it prevents the heart from contracting normally, leading to a progressive loss of the heart's ability to pump enough blood. play a role. Blood in the body. This chronic disease causes a worsening feedback loop that can only be slowed with available medical treatments, but there is no cure.

Researchers studying human tissue samples as part of a new study identified a type of fibroblast in the heart as the main cause of scar tissue formation in heart failure. To see if scarring could be prevented, the scientists turned to a mouse model of heart failure that had the exact same type of fibroblasts. They used a therapeutic protein – called a monoclonal antibody – that successfully blocked the formation of this harmful type of fibroblast, reducing scar tissue formation and improving heart function in mice. I did.

When scar tissue forms in the heart, its ability to heal becomes severely impaired or impossible. Heart failure is a serious problem in the United States and around the world, affecting millions of people. While current treatments can help reduce symptoms and slow progression, there is a great need for better treatments that actually halt disease progression and prevent the formation of new scar tissue that causes loss of heart function. It is being We hope that our research will lead to clinical trials investigating this immunotherapy strategy in heart failure patients. ”

Cory Rabin, MD, cardiologist, senior author, and professor of medicine in the cardiovascular division of WashU Medicine

Fibroblasts play many roles within the heart, and it has been difficult to dissect the differences between different populations of these cells. Some types of fibroblasts support the structural integrity of the heart and maintain good blood flow through the heart's blood vessels, while other types promote inflammation and the development of scar tissue. I will. Only recently, with the widespread availability of state-of-the-art single-cell sequencing techniques, scientists have been able to identify which cell groups are which.

“These different types of fibroblasts may lead to therapeutic strategies that specifically block the types of fibroblasts that promote scarring and protect the fibroblasts that maintain the structure of the heart so that it does not burst. “It highlights the newly recognized opportunities that exist,” Lavigne said. “Our study suggests that the fibroblasts that promote scarring in injured hearts are very similar to fibroblasts associated with cancer and other inflammatory processes. This opens the door to immunotherapy that can potentially stop inflammation and the resulting scar tissue.”

The research team, co-led by Juned Amrut, a graduate student in Lavigne's lab, used genetic techniques to show that a signaling molecule called IL-1beta drives fibroblasts to destroy scar tissue in heart failure. It has been demonstrated that it is important in the series of events that lead to the formation of With this in mind, they tested a mouse monoclonal antibody that blocks IL-1beta and found that it had a beneficial effect on the hearts of mice. Mouse monoclonal antibodies were provided by Amgen, whose scientists are also co-authors of the study. Monoclonal antibodies are laboratory-made proteins that regulate the immune system. The treatment reduced the formation of scar tissue and improved the pumping capacity of the mice's hearts, as measured by echocardiograms.

At least two FDA-approved monoclonal antibodies – canakinumab and rilonacept – have the potential to block IL-1 signaling. These immunotherapies are approved to treat inflammatory diseases such as juvenile idiopathic arthritis and recurrent pericarditis, an inflammation of the sac surrounding the heart.

One of these antibodies is also being evaluated in clinical trials for atherosclerosis, the buildup of plaque that causes hardening of the arteries. The trial, called CANTOS (Canakinumab Anti-Inflammatory Thrombosis Outcomes Study), showed benefits for study participants with atherosclerosis.

“Although this trial was not designed to test this therapy for heart failure, there are hints in the data that monoclonal antibodies may be beneficial for heart failure patients,” Rabin said. “Secondary analysis of data from this trial showed that this treatment was associated with a significant reduction in heart failure hospitalizations compared to standard care. Our new study explains why. It might be helpful.”

Still, the IL-1 antibodies used in the CANTOS study had side effects, including an increased risk of infection, and more targeted antibodies that specifically block IL-1 signaling in cardiac fibroblasts are being tested. Researchers say it could probably be reduced if used. .

“We hope that combining all of this evidence, including our work on the IL-1beta pathway, will lead to the design of clinical trials specifically testing the role of targeted immunotherapy in heart failure patients,” Lavigne said. said.