Inflammation Reducing Antibody Could Serve as Cardio-Immunotherapy for Heart Failure Patients

Following a heart attack, viral infection, or other injury to the heart, scar tissue frequently forms in the heart muscle, disrupting the heart’s normal contractions and contributing significantly to heart failure—the gradual loss of the heart’s ability to pump adequate blood to the body. This chronic condition creates a worsening feedback loop that can only be mitigated by existing medical therapies, as there is currently no cure. A new study now indicates that a type of immunotherapy—similar to those approved by the Food and Drug Administration (FDA) for treating inflammatory conditions like arthritis—may also serve as an effective treatment approach for heart failure.

In this study, researchers from Washington University School of Medicine in St. Louis (St. Louis, MO, USA) examined human tissue samples and identified a specific type of fibroblast cell in the heart as the primary agent responsible for scar tissue formation in heart failure. Fibroblasts perform various roles within the heart, and distinguishing between different populations of these cells has proven difficult. Certain fibroblast types contribute to the heart’s structural integrity and ensure proper blood flow through its vessels, while others promote inflammation and scar tissue development. Only recently, due to the availability of advanced single-cell sequencing technologies, have scientists been able to identify which cell groups perform these distinct functions.

Image: Untreated mice develop major scarring after cardiac injury (purple tissue, left) while treated animals show much less scarring (right) (Photo courtesy of WashU Medicine)

The research team utilized genetic methods to show that a signaling molecule called IL-1 beta plays a crucial role in the sequence of events that drives fibroblasts to produce scar tissue in heart failure. To explore the possibility of preventing scar formation, the scientists used mouse models of heart failure containing the same type of fibroblasts. They administered a therapeutic protein known as a monoclonal antibody that inhibits the development of this detrimental fibroblast type. Monoclonal antibodies are lab-manufactured proteins that can modulate the immune system. In the study published in the journal Nature, the researchers tested a mouse monoclonal antibody that blocks IL-1 beta and observed positive outcomes in the hearts of the mice. This treatment decreased scar tissue formation and enhanced the pumping efficiency of the mouse hearts, as measured by echocardiography. At least two FDA-approved monoclonal antibodies—canakinumab and rilonacept—are capable of blocking IL-1 signaling. These immunotherapies have been approved for the treatment of inflammatory disorders such as juvenile idiopathic arthritis and recurrent pericarditis, which involves inflammation of the sac surrounding the heart.

“After scar tissue forms in the heart, its ability to recover is dramatically impaired or impossible,” said cardiologist and senior author Kory Lavine, MD, PhD, a professor of medicine in the Cardiovascular Division at WashU Medicine. “Heart failure is a growing problem in the U.S. and globally, affecting millions of people. 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.”