Inhaled EP4 receptor agonists for the treatment of idiopathic pulmonary fibrosis

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This project aims to deliver a novel drug candidate for the treatment of idiopathic pulmonary fibrosis (IPF), a debilitating and fatal disease for which few treatment options are available. IPF is a chronic and progressive lung disease where excessive scarring occurs in the lung. This leads to stiffening of the airways, making it harder for the lungs to inflate and function normally, which causes severe shortness of breath. Patients with IPF experience worsening symptoms over time that prevent them performing activities that many of us take for granted, including daily tasks such as washing and dressing. For many people this progression is rapid, and people die early. In fact, with an average survival time of only 3 years from diagnosis, IPF is worse than most cancers. Diagnosis of IPF is a complex and lengthy process, but current estimates suggest that 18 people in every 100,000 suffer from it in the UK. Wound healing is a normal process where naturally occurring substances (or growth factors) in the lung stimulate regrowth of cells to repair the damaged area. For some reason, in IPF this process is not properly regulated, so cell growth continues unchecked resulting in the characteristic scarring of the lungs. Currently two anti-cancer drugs are used in IPF in an attempt to prevent this cell growth, but they only inhibit some of the growth factors that stimulate repair, so are not very effective. They are also swallowed drugs and have unwanted effects on other parts of the body. This is particularly bad in the gut where they can cause diarrhoea that is so severe that many patients chose to stop taking their medicines. Despite ongoing research in this area, effective medicines to treat IPF remain elusive, highlighting the need to explore new ways of treating this disease. We have identified a novel approach to treat IPF. By specifically activating beneficial pathways in lung cells we will counteract the unregulated wound healing stimulated by all growth factors involved in IPF. We will do this by switching on a particular protein on the surface of lung cells known as the EP4 receptor. We have already shown that activation of this receptor is able to robustly inhibit several key processes involved in scarring, and therefore has the potential to treat this debilitating disease. In addition to improving the effectiveness of existing IPF medicines, we also want to make them safer by reducing the severe side effects linked to them. To do this, we plan to develop a medicine that can be taken using an inhaler, similar to other lung diseases like asthma. This will allow us to deliver our medicine directly to the lung where they are needed, without reaching the rest of the body where they may cause unwanted effects. This project has been designed and submitted by researchers at the University of Nottingham who have significant expertise in making drugs for lung diseases, having successfully brought new drugs to market for asthma and chronic obstructive pulmonary disease (COPD). Our aim is to build on these successes and develop a novel, effective and safe medicine for IPF patients.