67th Edition – April 2017

ADVANCE project publishes Code of Conduct to improve future vaccine studies

Monitoring the benefits and risks of vaccines is a complex and critical activity which involves multiple participants. Decisions that have to be made at the planning stage of such studies are complex and numerous, which can prove challenging in situations where rapid action needs to be taken and a benefit/risk assessment is urgently needed. To address that challenge, IMI’s ADVANCE project published a Code of Conduct: a document which contains a set of guiding principles for the multiple decisions that need to be taken at all stages of the planning, design, conduct and reporting of future studies. If adopted by all partners involved in a study, these recommendations will not only make it easier for the partners to collaborate, but will also give confidence to health professionals and the public about the quality of their results.

The ADVANCE Code of Conduct, now available in the journal Vaccine, was developed by members of a wide range of different organisations including regulatory and public health authorities, vaccine manufacturers and academic organisations. Its development was guided by three core and common values (best science, strengthening public health, transparency), and a review of existing guidance and relevant published articles. The document includes 45 recommendations in 10 topics: scientific integrity, scientific independence, transparency, conflicts of interest, study protocol, study report, publication, subject privacy, sharing of study data, and research contract. In the publication, the authors said they hope that ‘adoption of the ADVANCE Code of Conduct by all partners involved in a study will facilitate and speed-up its initiation, design, conduct and reporting'. The Code of Conduct is one of the four components of good practice guidance for vaccine studies, which will also include recommendations for good governance, quality management and communication on vaccine safety. This important deliverable of the ADVANCE project aims to pave the way for a European framework capable of rapidly delivering reliable data on the benefits and risks of marketed vaccines.

COMBACTE-NET sheds light on body’s defence systems

The case of a young girl with a life-threatening infection has shed new light on how the body prevents common bacteria from causing serious disease. The research, funded in part by IMI through the COMBACTE-NET project, is published in the prestigious journal Cell. Staphylococcus aureus is a common bacterium that can be found on the skin and in the nostrils of most healthy people. However, it can also cause infections and in some cases, these infections can result in serious illness. This case revolves around a young girl who, at the age of three months, was admitted to intensive care with pneumonia and sepsis caused by S. aureus. Fortunately, doctors were able to treat her and she made a full recovery. Nevertheless, her case was puzzling because she did not have any risk factors (e.g. a weakened immune system) for serious S. aureus infection, and no-one else in her family appeared to be affected. A DNA analysis revealed that she had a mutation in a gene that codes for a protein called TIRAP, which plays a key role in the ‘innate’ immune system that develops before we are born and helps the body to identify invaders. However, seven members of her family turned out to share this mutation, yet had no history of falling ill with S. aureus infection. Further research revealed that the family members were protected from infection by their acquired immune defences, which develop after birth and build up over time as and when we are exposed to new bugs. In contrast, the patient’s immune system had not learnt to recognise staphylococcal bacteria, leaving her vulnerable to infection. ‘Her illness likely resulted from failures in both lines of immunity,’ explained the lead author of the paper, Jean-Laurent Casanova of the Howard Hughes Medical Institute. ‘In her family, the second layer of defence compensated for genetic defects in the first. More broadly, it offers insight into how two people with the same infection, and even the same DNA, can have very different illnesses.’

 - Read the press release from the Rockefeller University

Parkinson’s UK creates ‘virtual biotech’ based on European Lead Factory results

Parkinson’s UK has allocated GBP 1 million (approx. EUR 1.2 million) for the creation of a virtual joint venture biotech company with the University of Sheffield to further develop compounds that were identified through the European Lead Factory and that could prove useful in the hunt for a treatment for Parkinson’s disease. The European Lead Factory comprises a collection of over 400 000 compounds from public and private sources as well as a state of the art screening centre. Richard Mead of the University of Sheffield turned to the European Lead Factory for help identifying compounds that could prove effective against a drug target involved in oxidative stress, which plays an important role in Parkinson’s. The European Lead Factory set up and ran the screens, and the results were so interesting that Parkinson’s UK decided to set up a ‘virtual biotech’ company, Keapstone Therapeutics, to support further work on the compounds identified. According to Richard Mead, the results would have been ‘absolutely impossible’ without the European Lead Factory. ‘We made incredible breakthroughs!’ he said. ‘Many, including ourselves, have screened various commercial and academic libraries, but never found anything useful. The diversity and quality of the Joint European Compound Library is not available anywhere else.’ Meanwhile, Arthur Roach, Director of Research at Parkinson’s UK added: ‘We were convinced that these early results are really good starting points in developing new treatments for Parkinson's and formed Keapstone Therapeutics as a new way to further this research.’

 - Read Richard Mead’s testimonial on his experience of working with the European Lead Factory

 - Read the Parkinson’s UK press release

IMIDIA identifies signs of diabetes risk

Researchers from IMI’s IMIDIA project have uncovered clues that could help to identify people at risk of developing diabetes. Diabetes arises when the beta cells of the pancreas fail to produce enough insulin to regulate blood sugar levels correctly. There is currently no cure for diabetes, and a lot of research focuses on improving our understanding of the underlying causes of the disease. Writing in the journal Molecular Metabolism, the researchers explain how they have identified a gene called Elovl2 that appears to play a key role in insulin secretion. According to the team, Elovl2 codes for an enzyme that makes a poly-unsaturated fatty acid called DHA. The researchers confirmed its role in insulin secretion in both mice and human cell lines. A second paper, in Cell Reports, demonstrates that the levels of certain lipids (fats) in people’s blood plasma appear to be raised up to nine years before diagnosis. Scientists from the Swiss Institute of Bioinformatics (SIB) were involved in both papers. In a press release, they point out that the studies brought together academic teams, pharmaceutical companies, and a small to medium-sized enterprise (SME), and that the results were cross validated through the IMIDIA project. ‘The findings therefore highlight the instrumental role of public-private partnerships, such as the IMI, in enabling such advances and improve public health,’ they conclude.

K4DD project results in a PhD thesis

Binding interactions between neuropeptides (the body’s neural signalling molecules), drugs and their target molecules were the focus of the first PhD thesis defence resulting from IMI’s K4DD project. Indira Nederpelt of Leiden University was the author of the thesis which has already resulted in six peer-reviewed publications, with more to come. The thesis has helped expand the toolbox of available methods which allow more accessible measurements of how drugs and their target molecules interact in the body. According to Ad IJzerman of Leiden University, K4DD’s managing entity, ‘Indira’s study falls perfectly within K4DD's ambition to transform binding kinetics into traditional, indispensable, drug discovery parameters and thereby improve the success rate of drug discovery in the future.’ The main goal of the K4DD project is to improve our understanding of how potential drugs bind with their target, and develop methods and tools to allow researchers to study drug-target interactions with greater ease. An important part of the project is its educational programme, which has funded more than 20 post-docs and PhD students in the last five years. The programme has provided fellows with the opportunity to gain a thorough understanding of the connection between drug discovery and drug development by offering them an extensive drug discovery course and several binding-kinetics-oriented symposia. Fellows also got the opportunity to improve their soft skills by taking a scientific writing course, career workshops and a presentation workshop. Several more PhD theses are expected to be successfully defended by the end of this year.

EU-AIMS builds one of world’s richest autism databases

The value of IMI projects goes beyond their immediate scientific discoveries. Outputs often include large databases which are a goldmine of data for future research. IMI’s EU-AIMS project is an excellent example. The project has developed a large autism database, one of the richest of its kind in the world, which has the potential to drastically change the knowledge base for autism. The database contains comprehensive medical information on 450 people with an existing diagnosis of autism spectrum disorders (ASD) and 300 babies with a high risk of developing autism. This data is further combined and compared to 450 individuals with either typical development or various forms of intellectual disabilities. All this data was gathered through two big clinical studies within the EU-AIMS project: the Longitudinal European Autism Project (LEAPS) and Eurosibs. All the study participants were very comprehensively characterised in terms of their clinical profile, behaviour, family history, medical history, cognitive profile, electroencephalography (EEG), various brains scans, and genomics. ‘The scale and level of phenotyping of LEAPS is unprecedented in the world,’ said the project coordinators. ‘Conducting a study of this scope would most likely not be possible without the IMI funding.’

The database is already being used by EU-AIMS researchers to identify biological clues which could help stratify autism patients in order to improve future clinical trials and develop more personalised treatments. Additionally, EU-AIMS is already sharing the database with five large international organisations with which it has signed data sharing agreements. The database will open to the entire scientific community in 2020. Preregistration will be required to access the data in order to increase transparency and reproducibility of findings. The building of the database fits perfectly within the overall goal of the EU-AIMS project, which is to generate tools that will enhance our understanding of ASD and ultimately pave the way for the development of new, safe and effective treatments for use in both children and adults.