A new study from the Washington University (WashU) School of Medicine in St. Louis suggests that existing immunotherapy drugs already used to treat inflammatory conditions may offer a potential treatment for the millions of Americans living with heart failure, a condition now projected to affect one in four people during their lifetime.
Heart failure (HF) progressively weakens the heart’s ability to pump blood effectively. While it often develops after heart attacks or viral infections, the key culprit is scar tissue that forms in the heart muscle, interfering with normal contractions and degrading cardiac function. Current treatments can only slow the disease’s progression and manage symptoms —there is no cure.
The condition already affects nearly 7 million U.S. adults, with rates rising particularly among younger patients, according to the Heart Failure Society of America (HFSA).
This should be a “wake-up call” for the overall health care system, Dr. Biykem Bozkurt, an advanced heart failure and cardiac transplantation cardiologist and chair of the HFSA Data in HF Committee, said in a press statement, warning that “we need to address worsening trends in heart failure.”
Treating HF by Reducing Scar Formation
Published Wednesday in Nature, the new animal study highlights the damaging role of a type of fibroblast cell in heart tissue, which typically provides support to the contracting heart muscle. The findings suggest that targeting inflammation to treat tissue fibrosis could reduce HF-related scar tissue formation.
“After scar tissue forms in the heart, its ability to recover is dramatically impaired or impossible,” study senior co-author Dr. Kory Lavine, a cardiologist and professor of medicine at the WashU School of Medicine, said in a press release.
“There is a tremendous need for better therapies that actually stop the disease process and prevent the formation of new scar tissue,” he added.
Some fibroblasts promote inflammation and scarring, while others maintain essential heart structure and blood flow. Lavine’s team discovered that a signaling molecule called interleukin-1 beta (IL-1 beta) drives the harmful fibroblast activity.
Potentially Effective Drugs Already Available
When researchers blocked IL-1 beta using monoclonal antibodies in mouse models of heart failure, they saw reductions in scar tissue formation and improved heart function.
Drugs approved by the U.S. Food and Drug Administration (FDA) that block IL-1 beta already exist.
Two such medications—canakinumab and rilonacept—are currently used to treat inflammatory conditions. One of these drugs showed promising results in a previous trial for atherosclerosis, a condition in which plaque builds up in the arteries, with data suggesting it might help heart failure patients.
The researchers are optimistic about the potential for these treatments in heart failure patients.
“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,” Lavine stated in the press release. “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.”
Next Steps and Challenges
Researchers acknowledge some concerns about side effects, particularly the increased infection risk associated with IL-1 beta-blocking therapies. Lavine suggested that developing more targeted antibodies focusing on cardiac fibroblasts could help reduce these side effects.
As a next step, the research team hopes that their findings will pave the way for clinical trials investigating the efficacy of targeted immunotherapy in heart failure patients.
“We are hopeful that the combination of all of this evidence, including our work on the IL-1 beta pathway, will lead to the design of a clinical trial to specifically test the role of targeted immunotherapy in heart failure patients,” Lavine said.