• Fibrotic diseases affect hundreds of millions of people worldwide and cause common diseases such as heart, lung, liver and kidney failure
• Scientists discover that interleukin¹11 (IL11) is a critical protein that causes fibrosis and organ damage, overturning the existing misconception that IL11 is anti-fibrotic
• Ongoing drug development targeting at IL11 in Singapore to treat patients with a range of fibrotic and scarring diseases

Singapore, 13 November 2017 – Researchers from Duke-NUS Medical School (Duke-NUS) and the National Heart Centre Singapore (NHCS) have discovered that a critical protein, known as interleukin 11 (IL11) is responsible for fibrosis and causes organ damage. This finding runs contrary to a misconception long accepted by the cardiovascular community that IL11 is anti-fibrotic.

Previous research had suggested that IL11 reduced cardiac fibrosis. However, the new findings showed that this is a mischaracterisation. Instead, the team’s findings identified a specific pro-fibrotic role for IL11, and that this protein is also the master driver of fibrosis, which results in heart and kidney failure.

Fibrosis is the formation of excessive connective tissue, causing scarring and failure of bodily organs and the skin. It is the common cause of cardiovascular and renal disease, where excessive connective tissue destroys the structure and function of the organ with scar tissue. Compared to other Asians, American, and Europeans, Singaporeans have a higher prevalence of coronary artery disease, hypertension, and diabetes, the three most common diseases that lead to heart failure. In addition, kidney failure is an epidemic in Singapore and around the world. Fibrosis of the heart and kidney eventually leads to heart and kidney failure, thus this breakthrough discovery — that inhibiting IL11 can prevent heart and kidney fibrosis — has the potential to transform the treatment of millions of people around the world.

The international team, led by Professor Stuart Cook, Tanoto Foundation Professor of Cardiovascular Medicine, along with Assistant Professor Sebastian Schäfer, both from NHCS and Duke-NUS’ Programme in Cardiovascular and Metabolic Disorders, carried out the translational research to identify the key drivers of chronic fibrotic disease in heart, kidney and other tissues. The team also includes researchers from Harvard University and University of California, San Diego/UCSD (USA), Max Delbrück Center for Molecular Medicine/MDC-Berlin (Germany), London Institute of Medical Sciences/MRC-LMS and Imperial College London (the UK), and the University of Melbourne (Australia).

"Fibrotic diseases represent a major cause of illness and death around the world and these illnesses are poorly understood. The discovery that IL11 is a critical fibrotic factor is the type of breakthrough that the scientists and pharmaceutical companies have been searching for. It is an incredibly exciting breakthrough discovery,” explained the study’s senior author, Professor Cook, who is also Director, National Heart Research Institute Singapore.

“Currently, more than 225 million people worldwide suffer from heart and kidney failure and there is no treatment to prevent fibrosis. The team is at the stage of developing a therapeutic target that can inhibit IL11 and potentially offer hope to patients with end-stage heart and kidney failure,” shared Professor Terrance Chua, Medical Director, National Heart Centre Singapore.

“This therapeutic target for fibrotic diseases of the heart, kidney and lung may be exactly what we need to fill the unmet pressing clinical gap for preventing fibrosis in patients. We are proud to announce that the suite of intellectual property arising from this research has been licensed to a newly launched Singapore-funded biotechnology start-up Enleofen Bio Pte Ltd, which is co-founded by Professor Cook and Assistant Professor Schäfer,” said Professor Thomas Coffman, Dean of Duke-NUS Medical School.

The research was supported by the National Medical Research Council under its Singapore Translational Research award (NMRC/STaR/0011/2012), the National Research Council Singapore Centre Grant to the NHCS, Goh Foundation, Tanoto Foundation, National Heart, Lung and Blood Institute, UK (NHLBI 5R01HL080494), Howard Hughes Medical Institute, USA (HHMI), and the Fondation Leducq.

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Reference:

1. Interleukins are a group of proteins that handle communication between cells, and they regulate cell growth, differentiation and movement. They are particularly important in immune responses, inflammation and fibrosis.