Singapore Scientists Uncover New Drug Target to Treat Fibrotic Diseases

0
302

Researchers from Duke-NUS Medical School (Duke-NUS) and the National Heart Centre Singapore (NHCS) have discovered that a critical protein present in the body, known as interleukin 11 (IL11), has been determined to be responsible for fibrosis and widespread organ damage. It is also a viable drug target for therapeutic intervention.

The team, led by Professor Stuart Cook, has also spun off a company that is on the fast track towards developing drugs targeting IL11. Drugs in development have a strong potential of being able to either significantly slow down or stop fibrotic diseases and organ damage.

Professor Stuart Cook, Director of the Cardiovascular & Metabolic Disorders Programme in Duke-NUS Medical School and Principal Investigator of the study which uncovered the IL11 protein. Credit: Duke-NUS Medical School

Discovery and Significance of IL11

IL11 expression is normally very low in most healthy human tissues. While it is surprising that the importance of IL11 has been overlooked and misunderstood for so long, it has now been very clearly demonstrated. A protein known as transforming growth factor beta 12 (“TGFB1”) has long been known as the major cause of fibrosis and scarring of body organs, but treatments based on switching off the protein have severe side effects as TGFB1 is also responsible for other functions such as immunity. The scientists discovered that IL11, is even more important than TGFB1 for fibrosis and that IL11 is a much better drug target than TGFB1.

Biopsy samples from heart surgery patients were profiled genomically. IL11 levels are significantly elevated, with a strong correlation to fibroblast formation. Credit: Prof Stuart Cook and Asst. Prof Sebastian Schaefer from the Duke-NUS Medical School
IL11 was shown to be important for fibrosis downstream of many other drug targets including TGFB1, but is ultimately critical for fibroblast activation. Credit: Prof Stuart Cook and Asst. Prof Sebastian Schaefer from the Duke-NUS Medical School
Deactivating IL11 protected mice from fibrosis, while increasing production of IL11 resulted in the mouse dying from cardiovascular fibrosis. Credit: Prof Stuart Cook and Asst. Prof Sebastian Schaefer from the Duke-NUS Medical School

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.

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.

Commercial and Future Scientific Developments

Since IL11 is a therapeutic target for fibrotic diseases of the heart, kidney and other organs, it is a golden opportunity to fill the unmet pressing clinical gap for preventing fibrosis in patients. Professor Thomas Coffman, Dean of Duke-NUS Medical School, announced the commercial intent of the team related to the discovery of IL11:

“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, co-founded by Professor Cook and Assistant Professor Schäfer”

With luck on their side, drugs being developed should be approved by 2019, with phase 1 clinical trials beginning at the end of 2020.

While part of the team has gone on to commercialize drug development, progress in basic science is also still well underway. Back in the laboratory, everyone is hard at work studying IL11 and its link with lung, kidney and the heart diseases. It was also found that IL11 only acts at the protein production levels, but does not change the RNA, which the team is itching to study further.

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).