75th Edition – January 2018

DRIVE-AB recommends ecosystem approach to drive antibiotic development

A mix of economic drivers and incentives is needed to stimulate antibiotic development, according to the final report of IMI’s DRIVE-AB project. The report, based on input from diverse stakeholders, highlights four incentives that would be the most effective in stimulating the antibiotic pipeline while also ensuring that critical antibiotics are used sustainably and are accessible to all who need them. The incentives picked out by the report are:

• Grants: non-repayable funds for R&D given to academic institutions, companies and others;
• Pipeline coordinators: governmental or non-profit organizations that closely track the antibiotic pipeline (or subsets thereof), identify gaps, and actively support R&D projects both financially and technically to fill these gaps;
• Market entry rewards: a series of financial payments to an antibiotic developer for successfully achieving regulatory approval for an antibiotic that meets specific predefined criteria to address a defined public health need, with obligations for sustainable use, equitable availability and supply;
• Long-term supply continuity model: a delinked payment to create a predictable supply of important generic antibiotics.

All of the recommended incentives would include mandatory provisions for equitable access and sustainable use in order to ensure these critical medicines are available to patients who need them globally, and remain effective over time. ‘The models are meant to be complementary and don’t operate in isolation. Instead, they’re designed to form an ecosystem that maximizes R&D while ensuring access and sustainable use of new antibiotics over time,’ said Christine Årdal, DRIVE-AB partner and Senior Advisor at the Norwegian Institute of Public Health.

Read the project’s press release

IMIDIA identifies novel signature of type 2 diabetes

The IMIDIA consortium has identified a novel signature of 19 genes whose activity is faulty in people with type 2 diabetes. The findings are published in the journal Diabetologia. In people with type 2 diabetes, the islet cells in the pancreas do not respond adequately to produce the hormone insulin, leading to elevated blood glucose levels and an inability to keep blood glucose levels stable. The scientists arrived at the signature after analysing and comparing gene activity levels in the largest collection of pancreatic islet cells from diabetic patients, people with pre-diabetes, and non-diabetic healthy individuals. Their work uncovered 19 genes with ‘dysregulated’ activity levels in the cells taken from people with type 2 diabetes. Of these, 10 had been identified in previous research, but 9 had never been picked up as being dysregulated in pancreatic islets before. Interestingly, the genes are not dysregulated in cells taken from people with pre-diabetes, suggesting that their altered activity levels are the consequence of, rather than the cause of islet cell failure. ‘We believe that our data provides novel molecular insights into what is going wrong in diabetic beta cells and sets new standards for how studies in this field shall be carried out in the future,’ said Michele Solimena of Dresden University of Technology, one of the leading investigators of the study. ‘Ultimately, we are confident that our approach will provide a new view for how exposure of beta cells to nutrient overload wears their function overtime, hence impairing their ability to satisfy the excessive demand of insulin to maintain metabolic homeostasis.’ Looking to the future, the researchers are keen to find out which genes are dysregulated before the onset of diabetes; this is a focus on the new IMI project RHAPSODY.

K4DD findings suggest new strategy for drug discovery

IMI’s K4DD project has shed new light on the factors that influence interactions between medicines and their targets. The findings, published in Nature Communications, could open up new avenues for drug discovery. Drugs work by binding with proteins that are implicated in disease and so preventing them from working. Much drug discovery work focuses on optimising the interactions between drugs and their targets. For a long time, researchers thought that the more tightly a drug binds with a target protein, the more effective it will be. The K4DD project set out to study in detail the kinetics of the interactions between drugs and targets. In this paper, the team applied state-of-the-art experimental and computational approaches to study the kinetics of anti-cancer medicines designed to block the action of a drug target called heat shock protein 90 (HSP90). Blocking the action of HSP90 can disrupt the cell cycle and so stop the growth of cancerous tumours. X-ray crystallography revealed that the binding pocket of HSP90 is lined by a region that can take the shape of a helix or loop, depending on the inhibitor under study. Notably, the drugs that bind with the comparatively flexible helix remain bound for longer. ‘We were really surprised when we found out that an important contributor to the long residence times was the greater mobility of the helical region of the binding pocket when the inhibitor bound,’ said Rebecca Wade of the Heidelberg Institute for Theoretical Studies, one of the co-authors of the paper. Using as an analogy a ski boot with an adaptable inner liner that continually adjusts to the foot, rhe researchers suggest that scientists can therefore consider less rigid protein targets and identify molecules that stabilise more mobile forms of the protein upon binding.

We are more prepared for future Ebola outbreaks – an interview with the Mofina project coordinator

IMI’s Mofina project developed a portable device which can test for deadly Ebola in 75 minutes or less, eliminating the need to take suspected Ebola patients to treatment centres far away of their communities. In an interview with the IMI Programme office, the project’s coordinator, Edmund Newman of Public Health England, explains how Mofina’s success will save lives, and help contain future outbreaks. ‘We now have a portable platform for testing all of the different types of Ebola virus that can run on a battery pack for up to 8 hours,' said Newman. 'It is a mobile platform that will give you a test result for all different types of Ebola within just over an hour, 75 minutes. It doesn’t require a big lab set up in the middle of the field somewhere. It is literally a finger prick of blood into an automated machine that is not much bigger than a shoe box and so it can easily be carried around and taken to the patient for testing. The device has been fully validated and verified for all the strains of Ebola that it tests for. It is commercially available and ready for the next outbreak.'

Read the full interview

APPROACH screens first patient

IMI osteoarthritis project APPROACH has screened the first patient in a clinical study on osteoarthritis of the knee that will pave the way for more personalised treatments for the disease. Over the next two years, 300 patients across Europe will undergo assessments on pain, mobility, cartilage and bone condition, and inflammation. Information gathered will help the project to identify biological markers (biomarkers) of disease progression. ‘Currently, all osteoarthritis patients are treated the same. The quality of clinical trials and personalised treatments by doctors will improve tremendously when disease subtypes can be diagnosed. Biomarkers will help to push this forward,’ said Anne Karien Marijnissen, coordinator of the APPROACH clinical study. The project’s seven-strong Patient Council was influential in the set up of the clinical study, collaborating on communications and study design (especially with reference to the burden on study participants) and reviewing the research protocol and patient informed consent forms.

RADAR-CNS recruits first participants in depressive disorder study

IMI’s RADAR-CNS project has recruited the first participants in the depression component of its study. The aim of RADAR-CNS is to develop new ways of measuring major depressive disorder, epilepsy and multiple sclerosis (MS) using wearable devices and smartphone technology. The first depression study participants have now received FitBit Charge 2 devices as well as smartphone apps. The participants will wear the FitBit for up to 24 hours a day, allowing it to capture information on their heart rate, sleep quality, and physical activity levels. Every few weeks, they will answer a short series of questions via the RADAR-CNS apps. Faith Matcham, post-doctoral research associate at RADAR-CNS, hopes to recruit around fifty more people over the coming months. ‘We’re so excited to be starting recruitment – this study will provide important information about how useable the RADAR-CNS platform is, as well as providing us with data which might be invaluable for improving our understanding of the course of major depression,’ she said. The epilepsy component of the study got underway in June last year, and the project team hopes to start recruitment for the multiple sclerosis study soon.

Thanks to EMTRAIN, we got out of our ivory towers – an interview with project coordinators

EMTRAIN established a pan-European platform for education and training covering the whole life cycle of medicines research, from basic science through clinical development to pharmacovigilance. In an interview with the IMI Programme Office, industry co-coordinator Matthias Gottwald of Bayer and academic coordinator Michael Wolzt of the Medical University of Vienna, explain what the project achieved and how it benefitted both industry and the academic community. ‘Thanks to this project, the academic community had a great opportunity to get out of their ivory towers and see what the industry actually does,’ said Wolzt. ‘We learned that we have a lot in common and that we can work together quite effectively.’

Read the full interview