Neutralising proteins targeting diseased lung cells can prevent and
reverse lung fibrosis in promising pre-clinical study.
Scientists have discovered a means of preventing and
reversing the effects of inflammation and scarring in a preclinical model of
idiopathic pulmonary fibrosis (IPF), a type of lung disease, by targeting
Interleukin 11 (IL11), a protein critical to fibrosis and inflammation. Their
findings, published in the journal Science Translational
Medicine, have implications for developing new drugs to treat
international collaboration led by Duke-NUS Medical School and National Heart
Centre Singapore (NHCS), and involving partner institutions in Germany, USA and
the UK, the researchers discovered IPF patients have abnormally high levels of
IL11 protein in their lung tissues and that patients with the highest levels in
their lungs get the most severe disease. Specific cells called myofibroblasts
in the diseased lung cause scarring and these cells are critically dependent on
IL11. When IL11 is turned off, these disease cells get turned off and lung
fibrosis is reversed.
contributes to lung fibrosis in a self-activating loop by stimulating
myofibroblasts that, in turn, produce and release even more IL11,” explained
NHCS researcher Dr Benjamin Ng, the study’s lead author. “We showed that IL11
is essential in causing lung fibrosis — in our lab experiments, we found that
anti-IL11 therapy protects the lungs from damage.”
triggered by a multitude of factors including age, genetics and environmental
factors, IPF is an incurable lung disease that leads to excessive fibrosis (or
scar tissue) around the air sacs in the lung, and eventually respiratory
failure and death. Current therapies are limited and have side effects and
while they slow the disease a little, they do not stop its progression.
lung scarring, called fibrosis, is a very serious condition that makes it
difficult to breathe. In our pre-clinical studies, we discovered that the IL11
protein is critical for fibrotic lung disease and that therapeutically
inhibiting IL11 can reverse lung disease,” said Professor Stuart Cook, the
senior and corresponding author of the study, who 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. Prof Cook’s research has previously uncovered the central
role of the IL11 protein in fibrosis and inflammation of the liver, kidney and
encouraging news for IPF researchers and patients, Prof Cook and his team have
developed bio-therapeutics called neutralising antibodies that work by
targeting and blocking IL11 to prevent the activation of myofibroblasts.
Promising pre-clinical studies revealed that these bio-therapeutics reversed
lung fibrosis and improved inflammation.
in lung disease highlights once again the pervasive role for IL11 in fibrosis
across organs. We successfully inhibited lung fibrosis by blocking IL11 using
an anti-IL11 therapy. This prioritises IL11 as an accessible drug target in
lung fibrosis,” Prof Cook stated.
to estimates, IPF affects over three million people worldwide, primarily people
over the age of 50 and more men than women. Professor Patrick Casey, Senior
Vice Dean for Research at Duke NUS, commented, “Given the increasingly ageing
populations across Asia, there will be 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 provides a promising direction.”
antibodies used by the research team have now been engineered for human use and
first safety clinical trials are planned for late 2020, with a view to clinical
trials in patients soon thereafter. Prof Cook’s team are continuing their
research efforts to better understand the contribution of IL11 in other
fibrotic diseases of the skin, pancreas, eye and bone marrow.
is also Director of the National Heart Research Institute Singapore and Deputy
Director (Clinical) of the SingHealth Duke-NUS Institute of Precision Medicine.
He is one of the co-founders of the biotechnology company Enleofen Bio Pte Ltd
in Singapore, which works to develop anti-IL11 therapies.
IL11 contributes to lung fibrosis in a self-activating loop by
stimulating lung myofibroblasts. (Photo credit: Dr Lim Wei-Wen)
Blocking IL11 using an anti-IL11 therapy prevents the activation of lung
myofibroblasts and reverses lung fibrosis. Picture at top is the control;
picture at bottom is after treatment with the antibodies developed by the
researchers. (Photo credit: Dr Benjamin Ng)
Reference: Ng, B., Dong, J., Viswanathan, S., & D'Agostino, G., et al. IL-11 is a therapeutic target in idiopathic pulmonary fibrosis. Science Translational Medicine. 2018. doi: 10.1101/336537
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