This protein is behind heart-scarring fibrosis

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A protein known as interleukin 11 (IL11) is responsible for fibrosis and causes organ damage, new research suggests.

Another protein, known as transforming growth factor beta 12 (“TGFB1”), has long been known to be the major cause of fibrosis and scarring of body organs, but treatments based around switching off the protein have severe side effects.

“The discovery that IL11 is a critical fibrotic factor represents a breakthrough for the field and for drug development…”

In the new research, scientists discovered that IL11 is even more important than TGFB1 for fibrosis, and that IL11 is a much better drug target.

Fibrosis is the formation of excessive connective tissue, causing scarring and failure of bodily organs and the skin. It is a very common cause of cardiovascular and renal disease, where excessive connective tissue destroys the structure and function of the organ with scar tissue.

Fibrosis of the heart and kidney eventually leads to heart and kidney failure, so the researchers’ findings have the potential to transform the treatment of millions of people around the world.

Compared to other Asians, Americans, and Europeans, Singaporeans have a higher prevalence of coronary artery disease, hypertension, and diabetes, the three most common diseases that lead to heart failure. Kidney failure is an epidemic both in Singapore and around the world.

The scientists carried out the translational research to identify the key drivers of chronic fibrotic disease in heart, kidney, and other tissues.

“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. It is an incredibly exciting discovery,” explains the study’s senior author, Stuart Cook, professor of cardiovascular medicine at the Duke-NUS Medical School and director of the 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 first-in-class therapies to inhibit IL11 and this offers hope to patients with heart and kidney disease,” says Terrance Chua, medical director at the National Heart Centre Singapore.

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“This therapeutic target for fibrotic diseases of the heart, kidney, and other organs 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 cofounded by Cook and assistant professor [Sebastian] Schäfer,” says Thomas Coffman, dean of Duke-National University of Singapore Medical School.

Additional researchers contributing to the study are from the Duke-NUS Medical School; Harvard University; University of California, San Diego; Max Delbrück Center for Molecular Medicine in Germany; London Institute of Medical Sciences/MRC-LMS; the Imperial College London; and the University of Melbourne.

The National Medical Research Council under its Singapore Translational Research award; the National Research Council Singapore Centre Grant to the NHCS; Goh Foundation; Tanoto Foundation; National Heart, Lung and Blood Institute, UK; Howard Hughes Medical Institute, USA (HHMI); and the Fondation Leducq funded the work.

Source: National University of Singapore