A cure for the incurable lung fibrosis?
Scientists have found a way to prevent and reverse the effects of idiopathic pulmonary fibrosis, making a breakthrough in the treatment of this previously incurable lung disease.
SINGAPORE| 26 SEPTEMBER 2019
Scientists from Duke-NUS Medical School and National Heart Centre Singapore (NHCS) recently worked together with partner institutions from Germany, USA and the UK to study idiopathic pulmonary fibrosis (IPF), a type of lung disease. They made a ground-breaking discovery that can potentially bring an end to this.
IPF is an incurable, life-threatening lung disease that is said to be a result of various factors such as old age, genetics and environmental factors. It is characterised by excessive fibrosis, which is the scarring of tissues, around the air sacs in the lung, and this will result in respiratory failure and ultimately, death. There are no treatments that can completely cure this disease currently, but there are, albeit limited and with side effects, therapeutic options that can serve to slow down the progression of the disease by a slight extent.
Through the research, researchers observed that IPF patients have abnormally high levels of Interleukin 11 (IL-11) in their lung tissues. IL-11 is a protein that is
instrumental in the formation of fibrosis and causing inflammation of lung tissues—it stimulates lung myofibroblasts, which are specific cells that cause scarring in diseased lungs, in a self-activating loop. The higher the levels of IL-11 there are in the patient’s lung tissues, the more severe the disease is. However, the researchers also found that when the IL11 gene is turned off, the disease cells, myofibroblasts, will be turned off as well. This will reverse lung fibrosis, which, in essence, means that the disease will be cured.
“IL-11 contributes to lung fibrosis in a self-activating loop by stimulating myofibroblasts that, in turn, produce and release even more IL-11 in a self-activating loop that, in turn, produce and release even more IL-11,” explained NHCS researcher Dr Benjamin Ng, the lead author of the study. “We showed that IL-11 is essential in causing lung fibrosis—in our lab experiments, we found that anti-IL-11 therapy protects the lungs from damage.”
“Progressive lung scarring, called fibrosis, is a very serious condition that makes it difficult to breathe. In our pre-clinical studies, we discovered that the IL-11 protein is critical for fibrotic lung disease and that therapeutically inhibiting IL-11 can reverse lung disease,” said Professor Stuart Cook, the senior and corresponding author of the study. He is the Tanoto Foundation Professor of Cardiovascular Medicine, Director of Duke-NUS Cardiovascular and Metabolic Disorders Programme, and Senior Consultant at the Department of Cardiology, NHCS. He is also the Director of the National Heart Research Institute Singapore and Deputy Director (clinical) of the SingHealth Duke-NUS Institute of Precision Medicine.
Together with his team, Prof Cook devised bio-therapeutics called neutralising antibodies that work by targeting and blocking IL-11 to prevent the stimulation of myofibroblasts, which would activate them to scar lung tissues. Pre-clinical studies have provided evidence that these bio-therapeutics did succeed in curing lung fibrosis and reduced inflammation of the lung tissues, and the antibodies used by the research team will be undergoing first safety clinical trials next year (planned: late 2020)—they have already been engineered for human use.
“Our work in lung disease highlights once again the pervasive role for IL-11 in fibrosis across organs. We successfully inhibited lung fibrosis by blocking IL-11 using an anti-IL-11 therapy. This promises IL-11 as an accessible drug target in lung fibrosis,” stated Prof Cook.
The team will further their research to investigate the effects of IL-11 in other fibroid diseases that occur in the skin, pancreas, eyes and bone marrow. As one of the co-founders of the biotechnology company Enleofen Bio Pte Ltd in Singapore which works to develop anti-IL-11 treatment options, Prof Cook has previously conducted researches in which he found out the effects of the IL-11 protein in fibrosis and inflammation of the liver, kidney and heart. Thus, with more research and better understanding of the effects of IL-11, he will be able to formulate evidence-based treatment options that can prevent and nullify fibroid diseases.
IPF affect more than three million people worldwide, with most of the sufferers aged above 50 years. It is also more prevalent among the male population. Professor Patrick Casey, Senior Vice Dean for Research at Duke-NUS, commented on this issue, saying, “Given the increasingly ageing populations across Asia, we could see an increase in the number of persons at risk and the incidence rate of IPF. That makes new avenues for treatment all the more critical, and this research appears to be moving us in a promising direction.”
The research paper was published in June 2018 on Science Translational Medicine.
This article was contributed by Ling Yi, an editorial intern at World Scientific Publishing Co. and a contributing writer for Asia-Pacific Biotech News. She is from Nanyang Girls' High School, has keen interest in learning more about life sciences and exploring literature, in both English and Chinese. She also enjoys studying different languages such as Japanese and Korean, and has a passion for dancing and reading.