113th Edition – June 2021

INNODIA diabetes findings prompt new research into other autoimmune diseases

Most research into autoimmune diseases focuses on the role of the immune system. But INNODIA research underscores the importance of studying the tissues under attack as well. Type 1 diabetes (T1D) occurs when the immune system attacks the beta cells in the pancreas. These cells are responsible for producing the hormone insulin, which regulates blood sugar levels. So far, research into autoimmune diseases has tended to focus more on the role of the immune system in driving the disease, and less on the role the target tissues (like the beta cells).

However, in research published in 2019, INNODIA researchers revealed major changes in gene activity levels in the beta cells. More recently, a new paper shows that as with diabetes, there are major gene activity changes in the target tissues of the other autoimmune diseases, such as the joints (rheumatoid arthritis), kidneys (systemic lupus erythematosus) and nerve cells (multiple sclerosis).

‘These observations suggest that future research on autoimmune diseases should focus on both the immune system and the target tissues, and on their dialog,’ the researchers conclude. ‘Discovering similar disease-specific signatures may allow the identification of key pathways that could be targeted for therapy, including the repurposing of drugs already in clinical use for other diseases.’

‘We must move away from the present “immune-centric-only” view of autoimmune diseases,’ explains the lead author of the paper, Professor Decio L. Eizirik of the Université Libre de Bruxelles. ‘Indeed, trying to understand these diseases focusing on the immune system only, and forgetting the target tissues, may be similar to attempting to fly a plane with only one wing.’

In summary, these papers show how results from an IMI project focusing on one disease area can have impacts in other disease areas.

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‘The IMI model aligns with our way of working’ – IMI Associated Partner TB Alliance

IMI Associated Partner TB Alliance is a non-profit organisation whose mission is the discovery, development and delivery of new and affordable tuberculosis (TB) drugs. In an interview with the IMI Programme Office, Director of External Affairs Ana Maria Harkins says that the partnership with IMI allows them to expand funding beyond a small and mostly static group of donors.

‘As a product development partnership, we leverage public-private mechanisms to accomplish our work, and the IMI model aligns well with our way of working,’ says Ms Harkin. ‘IMI brings together many of the main players and we greatly value the resources it makes available, as well as a platform to collaborate with industry, academia and the public sector.’

TB Alliance is involved in two IMI projects. Through ERA4TB, they are contributing two compounds for development, one of which is in Phase 1 trial. In EU-PEARL, they are involved in the work package dedicated to TB, where they provide regulatory expertise, knowledge and tools for community and patient engagement.

Asked about the benefits of working in a public-private partnership, Ms Harkin highlights the importance of tackling market failures like antimicrobial resistance. ‘Without political and financial incentives, the industry has little incentive to develop antibiotics,’ she says. ‘IMI provides resources to incentivise drug development, and an architecture that brings together an array of partners to contribute compounds, perform preclinical and clinical work, exchange data and research learnings and jointly work towards a set of agreed-upon outcomes.’

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IMI Associated Partner SFARI: ‘Collaborative efforts are invaluable for advancing autism science’

IMI Associated Partner the Simons Foundation Autism Research Initiative (SFARI) is a research programme whose mission is 'to improve the understanding, diagnosis and treatment of autism spectrum disorders by funding innovative research of the highest quality and relevance.' The project started working with IMI through the IMI1 project EU-AIMS, and is now an Associated Partner in the IMI2 project AIMS-2-TRIALS.

‘In addition to expanding and sharing our SPARK cohort — which will be a community of over 50 000 individuals with autism, and their families, for a majority of whom we will have genomic data — we have provided supplies of an experimental medication that is being tested in a clinical trial run by AIMS-2-TRIALS,’ says SFARI Deputy Director of Clinical Research, Paul Wang, in an interview with the IMI Programme Office. 

‘Autism is enormously complex, and we believe that collaborative efforts spanning academia, industry, and the non-profit sectors, are invaluable for advancing autism science. Indeed, we strive to have representation from all of these sectors in many of our own workshops and other initiatives,’ he says.

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COMBACTE-MAGNET adds to our understanding of how resistance emerges during infection

It is known that treating patients with antibiotics is associated with the emergence of resistance - and worse outcomes for patients. But how resistance emerges during infections remains poorly understood.

Now a study published in Nature Communications reports that rapid bacterial evolution interacts with host immunity to shape both the rise, and fall, of resistance during infection. This study was performed as part of the IMI COMBACTE-MAGNET project.

COMBACTE-MAGNET is working to find new approaches to combat antibiotic resistance. This new study highlights the need to understand better how our immune system works with antibiotics to suppress bacterial infections.

The research described in the article is part of the ASPIRE-ICU study, which stands for Advanced understanding of Staphylococcus aureus and Pseudomonas aeruginosa Infections in EuRopE – Intensive Care Units.

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Diabetes treatments set to get personal, thanks to new IT tool

Building on ground-breaking results from IMI diabetes projects, scientists are now working on a software tool that would identify what subtype of diabetes a patient has, and suggest which treatment would work best for them.

For many years, the medical world has recognised two main types of diabetes: type 1 and type 2. However, research funded in part by IMI through the BEAt-DKD and RHAPSODY projects paints a different picture, suggesting that there are not two subtypes of diabetes, but five. The scientists have since validated these initial findings in additional patient populations, and several studies are currently ongoing to test the effects of different treatments on the different diabetes subtypes.

Meanwhile, investigators have developed a software tool, which is currently used for research purposes and is soon to be implemented in the clinic, to allow doctors to identify which diabetes subtype the patient has. The researchers have received funding from other sources beyond IMI to carry out these additional studies. All in all, this story shows how IMI projects can deliver ground-breaking results, validate them, and turn them into a tool that can hopefully assist in providing the right treatment for the right patient at the right time.

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Drug safety academic programme expands to North America

Born out of an IMI project, EU2P have offered a growing suite of certified drug-safety education courses since 2009. They are now expanding beyond the EU.

EU2P was set up to provide a pan-European, fully-accredited (and EU-wide recognised) training programme that could supply the skills and qualifications needed for a growing and evolving field. The number and variety of courses on offer by EU2P have steadily grown, and they span the quick and generic, such as a two-hour online course on drug safety basics, to a European Masters and PhD programme. The programme is still managed by the original team, based in the Université de Bordeaux.

‘The enduring success of the programme is due to the continuous investment in the development of new courses according to the demand of pharmaceutical companies and international scientific societies,’ programme manager Karine Palin told the IMI Programme Office. ‘The crucial element is that trainees benefit from academic accreditation and therefore can be awarded ECTS (European credit transfer and accumulation system) credits following their assessment.’

Looking to the future, the EU2P team is now developing courses in drug safety targeting the North American pharmaceutical industry, with a new programme called Am2P (for American Program in Pharmacovigilance).

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The most objective measure of your sociabilty? It’s in your pocket

PRISM is in talks with the EMA on the use of data from smartphones and wearables as biomarkers of social functioning in neuropsychiatric disorders.

Measuring human social behaviour i.e. interactions with others, or activities outside the home, is usually done via a variety of methods that, despite being used widely in biomedical research, are plagued with problems: interviews, questionnaires and self-rating (or rating by a carer or family member) are subjective, qualitative and usually after-the-fact.

Smartphones and wearables are already collecting reams of data on our physical movements and social activities. The IMI PRISM project looked at which kinds of data from these devices could be considered reliable biomarkers of social functioning. The PRISM team found promising data that measures such as the number of phone calls made, chats, and number of places visited, can be used to better stratify participants. If this can be confirmed, it offers a way of significantly improving clinical trial outcomes, ultimately resulting in better treatments.

The PRISM team is currently in talks with the European Medicines Agency (EMA) to establish how they can successfully make this kind of digital phenotyping part of future clinical trials, alongside traditional data-gathering methods and assessments.

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Rift Valley fever: antibodies identified to help develop diagnostic tests

VHFMoDRAD has made progress in understanding how different antibodies can be useful for diagnosing and detecting Rift Valley fever (RVF) virus in animal and insect tissues. The findings bring us one step closer to the development of effective diagnostic tools.

There is a pressing need for diagnostic tests to detect viral haemorrhagic fevers including RVF, Ebola, Marburg and yellow and dengue fevers These diseases have many symptoms in common, a fact that makes it very hard to make a rapid diagnosis, something essential in an outbreak situation.

VHFMoDRAD carried out a study where they looked at how different antibodies can be useful for diagnosis and detection of RVF virus in tissues from animals or mosquitoes. The authors used several different antibodies, and found that antibodies against nucleoproteins can be a good tools to find infected cells in sheep and mice and antibodies against glycoproteins can be used to find infected tissues in insects. The findings are published in the journal Scientific Reports.

The aim of VHFMoDRAD is to develop rapid point-of-care (POC) diagnostic tools capable of identifying a number of viral haemorrhagic fevers. Ultimately, VHFMoDRAD will contribute to better preparedness for outbreaks of viral haemorrhagic fevers, and to capacity building in Africa.

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A one-stop-shop for disease-specific human stem cells allows scientists to focus on research

Induced pluripotent stem cells (iPSCs) can be generated from tissues of people diagnosed with certain diseases, as well as healthy people, and then used to generate specific cell-types, which can then be used by researchers to carry out experiments.

Making iPSC lines from scratch is laborious and complicated, and re-using existing cell lines is also fraught with challenges. To help fix these problems, in 2014 IMI set up EBiSC, the European Bank for induced pluripotent Stem Cells. A subsequent project, EBiSC2, builds on EBiSC’s work.

EBiSC allows researchers to deposit their cell lines into a centralised repository, and enables distribution to the wider scientific community via a public catalogue, along with their relevant datasets. In addition, EBiSC can also help with reprogramming, gene-editing and characterising new iPSC lines and sharing knowledge and best practices. Depositors retain full ownership rights on their lines and can continue using and sharing them as they choose. Customers can quickly access iPSC lines from the desired donor background, selecting for age, sex, disease or phenotype, among other things.

As the lines are listed on a public catalogue, the impact of their research is highly visible and publications and datasets are clearly linked to the relevant cell lines. The project is currently aware of more than 100 publications using EBiSC iPSC lines, with likely many more available and in progress.

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Solute carriers raise hopes as drug targets, but many products sold to study them don’t work

Solute carriers (SLCs) are proteins that bring nutrients and other substances across cell membranes. Any problems with how these proteins function can cause disease, and they are increasingly being considered as drug targets. Antibodies are powerful biological tools that can be used to study the function of SLCs, but despite the large number of commercial antibodies available to buy, the RESOLUTE team found that 80% don’t work against their purported target.

‘What we can do now is to raise awareness in the scientific community and antibody vendors. We need to work together to develop better tools. By recognising this need, we can then work on a solution,’ said RESOLUTE communications manager Álvaro Inglés-Prieto in an interview with the IMI Programme Office.

‘We currently generate material and protocols and will share them with the community. This effort still remains a great challenge, but we think we are on a good track and the first results indicate that our approaches are successful.’

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