- Sign up for our online events on IMI's impact on diabetes, dementia and data
- Researchers tackle the problems that plague pain drug research – an opinion piece by Pierre Meulien
- Machine learning models outperform traditional selection methods for recruiting osteoarthritis trial patients
- US regulator to expedite review of gut microbiome protector product from COMBACTE partner
- COVID-RED seeks volunteers to help answer key question: Can digital tech detect COVID-19 infection?
- Big data study leads to identification of blood biomarkers for Alzheimer’s
- Placebo response is affected by the drug you *think* you might be taking – especially if it’s an opioid
- Neuropathic pain was classified in a way that stymied research. Not any more
- Receptor in bladder could spell new drug target for urological diseases
Sign up for our online events on IMI's impact on diabetes, dementia and data
Registration is now open for a series of online events that will showcase IMI’s impact in three areas: diabetes, dementia, and data management. During the events, experts including patients will explore the challenges and demonstrate how IMI has contributed to moving these fields forward. Each event will also include time for a wider discussion, and all event attendees are encouraged to actively participate in this.
In addition to the events, IMI has created dedicated web pages on each impact area, featuring more information on the challenge, what IMI is doing about it, and success stories from IMI projects.
IMI's impact on diabetes
- 8 June 2021, 15:00 – 17:00 | Agenda and registration
- Impact web page
IMI's impact on data
- 9 June 2021, 14:00 – 15:30 | Agenda and registration
- Impact web page
IMI's impact on dementia
- 15 June 2021, 14:00 – 16:00 | Agenda and registration
- Impact web page
Registration for the events is free but obligatory.
Researchers tackle the problems that plague pain drug research – an opinion piece by Pierre Meulien
When it comes to what matters most to patients, the alleviation of pain is often top of the list. But developing new pain killers is far from easy, writes IMI Executive Director Pierre Meulien in a new opinion piece published on the IMI website. New pain drugs are urgently needed because current treatments rely on opiates that are linked to addiction, often come with intolerable side effects, and do not work for some patients. IMI’s pain projects are making progress in a number of ways.
For example, EUROPAIN highlighted the role of patient expectations in the placebo effect. ‘If a patient knows that the medication being evaluated is a painkiller, they are more likely to report that their pain symptoms have improved, even if they are in the placebo group,’ explains Dr Meulien. The EUROPAIN work subsequently influenced guidelines on the development of analgesics.
Elsewhere, IMI-PainCare is working on harmonising measures for patient-reported pain-related outcomes to help clinicians and drug developers better evaluate treatments, as well as biomarkers, tools and methods for new treatments for pelvic pain. Finally, NGN-PET, which finished recently, confirmed the role of neuron-glial interactions in the generation of a pain response and identified genes that appear to be involved, creating a new opening for potential new drug targets.
Find out more
- Read the opinion piece in full
- Watch IMI’s video on pain research
Machine learning models outperform traditional selection methods for recruiting osteoarthritis trial patients
Knee osteoarthritis occurs when cartilage in the knee gradually wears away, resulting in pain and stiffness. When running clinical trials for new treatments for osteoarthritis, researchers need to ensure they include the right patients, i.e. people whose condition is likely to get worse during the trial. This is because the condition of many trial participants does not change much during the trial anyway, making it hard to assess how effective a treatment is.
When researchers from the APPROACH project were selecting patients for a study to uncover biomarkers of osteoarthritis progression, they wanted to make sure they could select patients who will progress during the observation period.
To do this, they took data from two long-term knee osteoarthritis studies to identify the best performing machine learning models. They found that the model-based selection outperforms the conventional inclusion criteria, reducing by 20–25% the number of patients who show no progression. This result could lead to more efficient clinical trials. Their findings are published in the journal Scientific Reports.
Find out more
- Read the article in full
US regulator to expedite review of gut microbiome protector product from COMBACTE partner
The US Food and Drug Administration (FDA) has granted ‘fast track designation’ to Da Volterra’s DAV132 for the prevention of Clostridioides difficile infection (CDI). The FDA fast track designation is intended to speed up the review of drug candidates for treating or preventing serious conditions.
DAV132 is a first-in-class microbiome protector designed to inactivate antibiotics that are circulating in the colon and disrupting the gut microbiome. It is destined for use in patients for whom microbiome disruption can be life-threatening, such as those with cancer. The product was developed by French SME Da Volterra, which is a partner in IMI’s COMBACTE-NET project.
As part of COMBACTE-NET, Da Volterra is about to launch an international phase 3 clinical trial called MICROCARE to evaluate DAV132 in patients with haematologic malignancies. MICROCARE will assess the efficacy of DAV132 in protecting intestinal microbiome diversity, preventing intestinal colonisation with potentially pathogenic bacteria, preventing bloodstream infections, and improving overall survival.
It will build on the results of ANTICIPATE, a multi-centre, prospective, observational study conducted within COMBACTE-NET to identify microbial factors predictive of CDI, the results of which were published recently in Nature Communications.
Find out more
- Read the article in full
COVID-RED seeks volunteers to help answer key question: Can digital tech detect COVID-19 infection?
The COVID-RED project is calling on people in the Netherlands to join its study on the ability of digital devices to detect signs of COVID-19 before the user even starts to feel ill. One of the biggest challenges in controlling the spread of COVID-19 is the difficulty of identifying people who are infectious but don’t know it because they feel perfectly healthy. But what if digital technologies could detect subtle changes in our bodies and prompt us to get tested before we start to feel unwell?
Enter COVID-RED, which plans to answer this question. At the heart of the project is the Ava bracelet, a certified medical device that was initially designed to track fertility but has been adapted to pick up early signs of COVID-19 infection. In a pilot study, the bracelet picked up signs of infection two days before the first symptoms appeared in 71 % of cases.
Now, the COVID-RED project has launched a new study to test and refine the bracelet and its accompanying COVID-detection algorithm and app in a larger group of 20 000 people in the Netherlands. They opened recruitment on 26 March, and by 9 April had hit the 10 000 mark.
Now the project is working hard to achieve its goal of recruiting 20 000 people. Participants receive an Ava bracelet and they will have to wear it every night, then synchronise the data with a special app in the morning. Every two weeks they will also be asked to answer a few questions via the app. Finally, participants will be asked to send in a few drops of blood four times during the study. The project has developed extensive materials to support participants throughout the study.
Find out more
- Read the article in full
- Want to take part in the study? Find out how here (page in Dutch; participation is only open to people living in the Netherlands)
Big data study leads to identification of blood biomarkers for Alzheimer’s
EMIF’s datasets helped researchers identify plasma proteins that changed in the presence of traditional Alzheimer’s markers, opening new avenues of research.
A major output of EMIF is the Multimodal Biomarker Discovery (MBD) study, which brought together hundreds of samples from three groups of people: cognitively normal controls, those with mild cognitive impairment and those with confirmed Alzheimer’s disease. That study, which concluded that the presence of amyloid and APOE ε4 status play central roles in the disease, was intended to help other researchers in the hunt for diagnostic and prognostic biomarkers by allowing any researcher to access them via the EMIF-AD Catalogue.
Now, a team led by the University of Oxford has analysed the samples and data from the EMIF-AD MBD cohort and found that certain blood proteins can predict the presence of Alzheimer’s pathology without the need for invasive lumbar punctures, accurately discriminating between people with mild cognitive impairment and people with Alzheimer's disease.
The study, published in the journal Alzheimer's and Dementia, compared the blood plasma of 600 people with mild cognitive impairment or Alzheimer’s with over 370 of their unaffected peers. Using a technology called SOMAscan, which can measure over 4 000 different blood proteins in a single plasma sample, the researchers identified groups of proteins that changed in correlation with traditional markers of amyloid plaque, tau tangles and neurodegeneration. These proteins point to potential targets for further studies on the molecular basis of Alzheimer’s.
Find out more
- Read the article in full
Placebo response is affected by the drug you *think* you might be taking – especially if it’s an opioid
The EUROPAIN project showed that a cautious description of expected drug efficacy and side effects may reduce the placebo effect. The placebo effect, in which a fake treatment causes a patient’s condition to improve, can be a big obstacle in clinical trials. If the placebo response is large, it's harder to measure the real effect of a potential drug.
‘Before a patient participates in a clinical trial, they have to give their informed consent. You have to give them quite a detailed description of the drug they might get and the potential side effects,’ explains EUROPAIN coordinator Märta Segerdahl in an interview with the IMI Programme Office. In the data they looked at, some participants were told they could potentially receive a new type of drug that it is similar to a common non-steroidal anti-inflammatory drug that everyone has taken. Others were told that they could get a type of drug has also been used as an antidepressant. Another group was told they could receive a strong opioid-like compound. Patients in this last group had the largest treatment or placebo response. EUROPAIN research also revealed that if patients know how likely they are to receive the active drug, that can influence the placebo effect.
When ethics committees are assessing trials, they are normally keen for participants to know everything about the likelihood of receiving an active compound. This is changing, says Professor Segerdahl.
‘In ethics applications I and others have successfully argued against telling the investigators the likelihood of the patients getting an active treatment, and against including that information in the informed consent form that the patients have to complete. Convincing the ethics review board with this argument is not something that had necessarily been done previously.’
Find out more
- Read the article in full
Neuropathic pain was classified in a way that stymied research. Not any more
EUROPAIN’s evidence that neuropathic pain patients should be grouped by their pain perception and not the event that sparked it convinced the European regulator to change its guidelines. This helped spark renewed interest among big and small drug developers to restart the search for new pain treatments after decades of stalled efforts. In an interview with the IMI Programme Office, EUROPAIN coordinator Märta Segerdahl discussed the project’s impact.
The project gathered a large database of patients with neuropathic pain and profiled them in detail. They found that patients whose pain is elicited by close-to-normal temperatures and mechanical stimuli like needle pricking for instance would be more likely than other patients to respond to a drug called a sodium channel blocker.
‘For regulators to understand that there is a difference between these patients, we couldn’t just hypothesise, we had to be able to demonstrate it with data,’ explained Dr Segerdahl. ‘So we went to them with all the data and we were able to show them that the principle holds.’
At the time, the EMA were updating their guidelines on the development of new drugs for the treatment of pain in general and they included many of EUROPAIN’s points in the final draft. So has this triggered a revival in the pain research field?
‘Of course, it takes time because companies need to restart their research from square one, but there are more biotech companies and pain research companies looking into these new targets,’ says Dr Segerdahl. ‘I have been talking to small and large companies and the interest has really increased in the last five years. I think one can hypothesise that the efforts of EUROPAIN and the change in the guidelines, combined with increased awareness of the opioid epidemic, have really contributed to the increased interest.’
Find out more
- Read the article in full
Receptor in bladder could spell new drug target for urological diseases
Researchers from the IMI-PainCare project have found evidence that a receptor called σ1-R, or sigma-1, is present in the human urinary bladder, and suggest that the receptor could be targeted to increase the efficacy of pain drugs.
The burden of painful bladder and cystitis is huge, and it's a problem that disproportionately affects women. In a new report, IMI-PainCare researchers document the functional role of the sigma-1 receptor in cystitis by comparing responses in animal models, concluding that it could offer a potential new drug target for the treatment of diseases involving the urinary system.
They found that drugs that block the action of this receptor can improve the manifestations of cystitis. The paper concludes that this presents a potentially attractive new drug target for testing in human urinary bladder disorders for which there is currently no adequate treatment, and a sigma-1 antagonist called E-52862 is currently in Phase 2 studies in patients with neuropathic pain. The compound could be used together with morphine and would allow for lower morphine dosing, while at the same time decreasing inflammation, potentially enhancing recovery.
Find out more
- Read the article in full