IMI News
- Sophisticated computing and human cell cultures are helping minimise animal use in drug development – IMI's Pierre Meulien
- New project HIPPOCRATES sets sights on psoriatic arthritis
- PRISM 2 to build on PRISM’s ground-breaking social withdrawal work
- Now online – summary reports of our impact series events
News from our projects
- Study: face masks cannot replace swabs for testing COVID19 viral load
- Analysis suggests that as COVID spread, emergency dept. visits dropped
- By linking up hospitals, the study of antibiotics in drug-resistant infections just got easier
- Virtual control groups: shared, reused data could reduce animal use in drug safety studies
- Safe, potent and consistent vaccine batches – no routine animal testing required
Sophisticated computing and human cell cultures are helping minimise animal use in drug development – IMI's Pierre Meulien
IMI projects are using advanced computational analysis, human cell lines and tissues, and better models to ‘reduce, replace and refine’ the use of animals in research, writes IMI Executive Director Dr Pierre Meulien in a new opinion piece on the IMI website.
Since its inception, IMI has been fully committed to achieving the goal of humane experimentation, and IMI-funded projects have resulted in a number of innovations that are directly or indirectly contributing to reducing, refining and replacing (i.e. the ‘3Rs’) the use of animals in drug development.
In routine vaccine production, the current quality control approach requires large numbers of laboratory animals. IMI’s VAC2VAC project aims to provide data to support the ‘consistency approach’ for quality control that promotes the use of in vitro, analytical, non-animal based systems.
New in vitro models using human cell lines, tissues and organoids, from human induced pluripotent stem cells (iPSCs), are being developed and validated in a number of projects: ADAPTED used iPSCs to determine the effect of the APOE genotype on inflammation, for example, in in vitro models of Alzheimer’s disease – basically human brain cells in a dish.
Innovations in computer modelling mean predicting drug safety is increasingly done without the use of animals: For example, NEURODERISK created a prototype to carry out toxicity profiling using 3D models, a software tool that is freely available to the public.
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New project HIPPOCRATES sets sights on psoriatic arthritis
Psoriasis is an autoimmune disease that primarily affects the skin. However, 20-30 % of people with psoriasis develop a condition called psoriatic arthritis. Symptoms include pain, joint stiffness and fatigue, and it can dramatically impact the quality of life of those affected. Today, psoriatic arthritis is very hard to diagnose, and it is not possible to predict which psoriasis patients will go on to develop psoriatic arthritis.
The aim of HIPPOCRATES is to deliver knowledge and tools that will make it easier to spot the psoriasis patients who are at greatest risk of developing psoriatic arthritis, and diagnose them faster. In addition, the team hopes to make it easier to predict how fast a patient’s condition is likely to worsen, and which treatments are most likely to be effective for them. Finally, the team plans to probe the molecular basis of psoriatic arthritis – information that will aid in the development of much-needed new drugs to treat the condition.
The HIPPOCRATES project brings together 26 partners and is set to run for five years. It has a budget of just over EUR 21 million, half of which comes from IMI, and half of which comes in the form of in-kind contributions from the EFPIA companies in the project.
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PRISM 2 to build on PRISM’s ground-breaking social withdrawal work
Currently, neurological disorders are diagnosed primarily on the basis of patients’ symptoms, and not on the causes of the disease. Furthermore, many symptoms appear in a number of diseases, yet we don’t always know if the causes of a given symptom are the same across diseases or not. IMI’s PRISM project focused on social withdrawal, a common early symptom of many neurological disorders. Specifically, the project shed new light on the underlying causes of social withdrawal in schizophrenia and Alzheimer’s disease.
The goal of the PRISM 2 project is to build on the achievements of the original PRISM project. Specifically, it aims to validate PRISM’s findings on social withdrawal in schizophrenia and Alzheimer’s disease, and investigate whether they also apply to major depressive disorder.
Ultimately, the work of PRISM 2 should ensure that these findings will result in more accurate diagnoses and treatments for people with Alzheimer’s disease, schizophrenia and major depressive disorder.
PRISM 2 will run for 3 years and has a total budget of almost EUR 8 million, coming from IMI, EFPIA companies and an IMI2 Associated Partner. It was funded under IMI2 – Call 22, which was designed to provide additional support to certain existing IMI2 projects to allow them to build on their achievements and maximise the impacts of their work.
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Now online – summary reports of our impact series events
Looking for a quick summary of our impact series events? Check out our online summary reports:
“The best is yet to come” – diabetes impact event report
New ways of working - data impact event report
A radical, end-to-end approach – dementia impact event report
And if you want to find out more about what was said, simply follow the links at the bottom of the reports to get to the main event pages, where you can find all the presentations and recordings.
Study: face masks cannot replace swabs for testing COVID19 viral load
A team that included researchers from the DRAGON project has found that viral load is lower on face mask filters than on nasopharyngeal swabs. Face masks and personal respirators can help stop the spread of droplets that carry the SARS-CoV-2 virus, and while nasopharyngeal swabs are the most dominant method for the collection of samples for COVID-19 diagnosis, the DRAGON project wanted to know if filters embedded in this personal protective equipment could be used as a non-invasive way to collect samples for, say, at-home testing.
DRAGON conducted a study where they generated inactivated virus-laden aerosols and dispersed them onto filters within face masks. These laboratory-based tests could detect coronaviruses down to a level of 10 copies per filter. However, testing of around 45 clinical samples suggested that the viral load emitted in breath aerosols of most patients with COVID-19 fell below this threshold. The difference in detection of SARS-CoV-2 between filters and nasopharyngeal swabs suggests that the number of viral particles collected on the face mask filter was below the limit of detection for all patients except those with the highest viral load – which has been shown to peak just before the onset of symptoms. This indicates that face masks are unsuitable for replacing nasopharyngeal swabs in the diagnosis of COVID-19. However, it might yet be suitable for chronic infectious agents where pathogen release is sustained, rather than having a transient period of high emission followed by a rapid resolution.
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Analysis suggests that as COVID spread, emergency dept. visits dropped
The beginning of the coronavirus pandemic led people to stay away from emergency departments (EDs) in the UK, recent data analysis suggests, including those with urgent heart problems. And this in turn may have led to a spike in mortality, according to a new study supported by IMI project BigData@Heart.
The study, which was published in the journal Circulation: Cardiovascular Quality and Outcomes, analysed data gathered between March and April 2020 from the UK’s government statistics body, as well as a public registry that tracks emergency department visits, and ran a script to estimate the number of excess deaths. They estimate that during the initial phase of the pandemic, there was a drop of about 2 750 visits per week (a 35% decrease) for suspected cardiac disease.
Lead author Dr Michail Katsoulis said: "Our analysis suggested that one cardiac death might have been prevented or delayed for every additional 12 ED visits for suspected cardiac conditions." They arrived at the conclusion that there may have been as many as 232 more deaths per week early in the pandemic, compared to the pre-pandemic period.
As for the reasons people stayed away, no doubt fear of infection played a role. On top of that, public health messaging focused on encouraging people to put as little pressure on the UK’s national health service as possible.
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By linking up hospitals, the study of antibiotics in drug-resistant infections just got easier
Launched in 2014, the COMBACTE project’s CLIN-Net and LAB-Net network provides strong infrastructure to run clinical trials of new antimicrobial agents across multiple sites, and is the only one of its kind in the world, putting Europe in a leadership position in clinical research into infectious diseases.
The network was quickly put to use, allowing pharma partners in the project to test novel antibacterials faster, more effectively and more economically. As additional support, EPI-Net was established to meet the need for a comprehensive source of published data related to the epidemiological aspects of AMR.
Although CLIN-Net and LAB-Net were originally conceived to respond to the threat of AMR, they were involved in the PREPARE project, which focuses rapid scientific response to infectious disease threats. When COVID-19 emerged, the network was immediately used for finding suitable clinical sites in hospitals and primary care for COVID-19-related studies.
Looking to the future, the networks built under COMBACTE will gradually become a new entity called the European Clinical Research Alliance for Infectious Diseases (ECRAID). It will be a separate legal entity led by the key players of the COMBACTE networks, among others.
ECRAID will set up several perpetual observational studies (POS). The disease areas for which POSs are currently being established are infections picked up via ventilation in intensive care, as well as complicated urinary tract infections and yeast infections in new-borns, among others.
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Virtual control groups: shared, reused data could reduce animal use in drug safety studies
Before drugs can be tested in humans, medicines regulators require companies to assess the safety of a drug candidate in animal studies. Some animals are administered the compound that is being investigated at different doses, while another animal group is used as control, meaning they don't receive the drug candidate. These control groups have generated a lot of data, and IMI’s eTRANSAFE is deploying computer wizardry to bring this data together and use it to better understand and predict drug safety, resulting in safer drugs while reducing the number of animals used in research, part of a wider trend in biomedical research (see the 3Rs).
Specifically, they want to create ‘virtual control groups’ that could replace real ones in future studies. Since in a usual animal study, 25% of the animals are used as controls, the suggested approach has the potential to reduce the number of animals needed by a quarter. In the coming months, a proof-of-concept will be carried out using as many as 500 studies identified by the eTRANSAFE pharma partners. They will take already completed studies, replace the original control group with the virtual control group, and compare the findings. If the results are promising, the project will request a meeting with the European Medicines Agency to assess whether the virtual control group concept could satisfy the requirements for animal toxicology studies.
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Safe, potent and consistent vaccine batches – no routine animal testing required
Every single batch of human or animal vaccines that is manufactured must undergo a series of rigorous tests to ensure it meets certain standards for safety and potency. Today, many of these batch tests involve large numbers of laboratory animals. In addition to raising ethical questions, the testing process tends to be slow and expensive and the results are not always relevant and reproducible. In an interview with the IMI Programme Office, the VAC2VAC project explains how it is working to develop alternative batch tests that do not involve animals.
One highlight concerns a test for pyrogens (contaminants that could cause a fever) in a vaccine against tick-borne encephalitis virus (TBEV). The traditional test uses rabbits, but VAC2VAC further developed the monocyte activation test (MAT), a cell-based assay. The method was validated in GSK, the manufacturer of the vaccine, and implemented following approval by the competent authorities.
‘This is the first method within VAC2VAC to reach regulatory acceptance and implementation and thus represents an important milestone in our effort to implement the consistency approach,’ the project explains.
The project is also busy developing tests to assess the quality and quantity of antigens in a number of vaccines - antigens are a key component of vaccines as they trigger the immune response.
The project has generated a lot of interest globally, as evidenced during conferences where scientists from a developed as well as low and middle-income countries highlighted the widespread commitment towards the replacement of in vivo (animal) testing.
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