88th Edition – March 2019

Scientists identify culprit in organ scarring diseases

An international team of scientists has identified a protein that plays a key role in the organ scarring that is a characteristic of many chronic diseases including idiopathic pulmonary fibrosis (lungs), cirrhosis (liver), kidney fibrosis, systemic sclerosis (the skin), and graft versus host disease (gut). The findings, which suggest new avenues for treatments for these diseases, are published in the journal Nature. The study was funded in part by IMI through the RTCure project. Connective tissue cells called fibroblasts help to maintain the integrity of our organs and repair them when they are injured. Usually, once a wound has been healed, the fibroblasts dial down their activity and return to a resting state. However, in diseases such as those listed above, the fibroblasts are over-active, and produce excessive amounts of connective tissue. This results in organ scarring and impairs the ability of the organ to work correctly. In this latest study, researchers studied a protein called PU.1. In normal wound healing, the production of PU.1 is blocked, allowing the fibroblasts to return to a resting state. However, the researchers found that in people with diseases of the connective tissues, PU.1 is activated.

‘PU.1 binds to the DMA and re-programmes the connective tissue cells, resulting in a prolonged deposition of tissue components,’ explained Andreas Ramming of the Friedrich-Alexander-University Erlangen-Nürnberg in Germany, the lead researcher of the study. The team emphasises that PU.1 is not the only factor involved in fibrosis. However, the new findings highlight the central role it plays in the process. Moreover, they showed that deactivating PU.1 causes the fibroblasts to return to their resting state. ‘PU.1 is like the conductor in an orchestra,’ said Dr Ramming. ‘If you take it out, the entire concert will collapse.’ The researchers conclude that drugs to block PU.1 could represent an effective approach to treating a wide range of fibrotic diseases.

RADAR-CNS study reveals factors influencing digital technology use for depression

A new RADAR-CNS study reveals some of the factors that could influence the use of mobile technologies and wearable devices to track patients’ condition over time. The results of the study, published in the journal JMIR mHealth and uHealth will contribute to the outputs of the project. RADAR-CNS is working to develop new ways of monitoring major depressive disorder, epilepsy, and multiple sclerosis using wearable devices and smartphone technology. The hope is that these technologies would make it possible to detect changes in behaviour, sleep, or mood before the individual themselves is aware of it. This could help them to predict – or even avoid – a relapse. The project is working with patients to discuss their attitude towards the use of these technologies to monitor their condition. In this latest study, the project discussed the technologies with adults with experience of depression from Spain, Italy and the UK. In all three countries, the patients raised issues regarding their motivation levels, the potential impact of the technologies on mood and anxiety, aspects of inconvenience, and ease of use.

‘Since the very beginning of RADAR-CNS, we have been committed to integrating the views and perspectives of people living with multiple sclerosis, epilepsy and depression into the design of the mobile technology,’ said first author Sara Simblett of King’s College London. ‘Each health condition is likely to present different challenges and barriers, and depression presents its own particular factors affecting motivation and engagement. This study has provided us with valuable information that will help us to produce something that really works for people in their everyday lives.’

Join the iPiE project’s final event

IMI’s iPiE project on the impacts of pharmaceuticals in the environment will hold its final conference on 24-25 June in York, UK. Since its launch over four years ago, the iPiE project has worked to develop frameworks that utilise information from toxicological studies, pharmacological mode of action and computational tools to support intelligence-based environmental testing of pharmaceuticals in drug development and to prioritise legacy pharmaceuticals (those authorised prior to the 2006 enactment of Medicines Agency requirements) for targeted environmental risk assessment and/or environmental (bio) monitoring. The project’s closing event will act as a forum to disseminate the results of the project while also providing opportunity to others working on the prioritisation and intelligent assessment of pharmaceuticals, to present their work.

‘We brought target binding kinetics to the international research community’ – an interview with the K4DD project coordinators

Drugs work by binding with molecules in the body to either block or alter the action of the target molecule. IMI’s K4DD project improved our understanding of how potential drugs bind with their target, and developed methods and tools to allow researchers to study drug-target interactions with greater ease. These tools will help scientists to determine whether a drug candidate is likely to be safe and effective much earlier in the drug development process. In an interview with the IMI Programme Office, project coordinator Anke Mueller-Fahrnow of Bayer, and academic coordinator Ad IJzerman of Leiden University explain how the project transformed the field and could lead to more effective drugs in the future. ‘Thanks to K4DD, more and more scientists within pharma companies but also in academia are aware of the importance of binding kinetics,’ said Mueller-Fahrnow. ‘So something that has really been pretty exciting and novel ten years ago, is something that is now broadly appreciated and used in the drug discovery process.’

• Read full interview
• Visit the project factsheet and website