Researchers from the Duke-NUS Medical School and the National Heart Centre Singapore have made a medical breakthrough in the discovery of a protein that is primarily responsible for fibrosis. The crucial finding challenges conventional literature that the protein, known as interleukin 11 (IL11), is harmless and dormant.

This could potentially impact millions of lives globally as more effective treatments against fibrosis can be discovered.

“Fibrotic diseases represent a major cause of illness and death around the world. The discovery that IL11 is a critical fibrotic factor represents a breakthrough for the field and for drug development,” said Professor Stuart Cook, director of the National Heart Research Institute Singapore, who led the study.

Importance of addressing fibrosis in Singapore

Fibrosis is the production of excessive connective tissue in the body that acts against an injury, which causes tissue scarring and organ failure such as heart, lung, kidney and liver.

It is essential to address fibrosis, particularly in Singaporeans as they are at greater risk of heart failure than other parts of Asia. This is due to a higher prevalence of developing coronary artery disease, hypertension and diabetes. In addition, there is approximately one new patient with kidney failure every five hours – and the number is expected to rise due to the pervading diabetes.

Illustration of how IL11 is a crucial determinant of cardiovascular fibrosis. Photo credit: Professor Stuart Cook and Assistant Professor Sebastian Schaefer
Illustration of how IL11 is a crucial determinant of cardiovascular fibrosis. Photo credit: Professor Stuart Cook and Assistant Professor Sebastian Schaefer

Globally, there are more than 225 million people who suffering from heart and kidney failure, without proper prevention treatments against fibrosis. Thus, the research team is aiming to develop “first-in-class therapies to inhibit IL11”, to “offer hope to patients with heart and kidney disease,” remarked Professor Terrance Chua, medical director of the National Heart Centre Singapore (NHCS).

Breakthrough discovery: It’s IL11 – not TGF-β1 – that causes fibrosis

Scientists conventionally believed that another protein – Transforming Growth Factor Beta 1 (TGF-β1) – was the major cause of fibrosis. However, targeting TGF- β1 with drugs or antibodies has resulted in severe side effects such as chest infections or skin cancer.

The study published in Nature Medicine instead, showed that IL11 acts as the “master switch”, where fibrosis occurs due to the hindered production of collagen and contributing proteins as IL11 is switched off.

The first of its kind, five-year study looked at a large human study-size of 84 heart samples from patients who underwent open heart surgery at the National Heart Centre.

Moving forward, the 20-man research team hopes to provide more evidence to develop treatments to target IL11, as well as determine whether antibodies can prevent fibrosis or even reverse it.

“What we would really love to be able to do is to reverse it. So, if people have advanced fibrosis, that can be turned back and the organ can become healthy again. There is a precedent that that can work, particularly in the liver,” commented Professor Stuart Cook, who led the research team, also the director of the Duke-NUS Medical School’s Cardiovascular and Metabolic Disorders Programme.

The team, including researchers from the United States, the United Kingdom, Germany and Australia, will be applying for drug approval for the antibodies in 2019, with plans to begin clinical trial on 20 to 30 people by 2020. MIMS

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