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Unravelling the enigma of autoimmune diseases

Diseases that involve the immune system going rogue share common molecular patterns - we’re slowly but surely teasing them out.

By Pierre Meulien, IMI Executive Director

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Image by Anna Schvet/Pexels

 

We like to think of the immune system as this surveillance mechanism for the body that’s standing guard, ready to weed out and kill anything harmful. But for many people, it doesn’t work that way; deregulated, the immune system can have devastating effects. With an autoimmune disorder, it fights our own tissue instead of protecting it. And while we might have some success in treating the symptoms, we are largely in the dark as to why treatments work for some and not for others, as well as what triggers the disease in the first place. Millions of Europeans suffer from these particularly debilitating diseases, for which the financial burden on our health systems is estimated to be over EUR 100 billion per year.

Deciphering the basic drivers of autoimmune diseases

Autoimmune diseases are a related group of conditions that have many features in common, and for which therapies that are considered successful are often only successful for a minority of people with the same symptoms. Immune therapy based on blocking the action of tumour necrosis factor (NFT) was developed about 20 years ago, and the results for a subset of patients were indeed remarkable. However, in a large percentage of cases the therapies had zero positive effect. Scientists have no way of predicting which patients will respond positively to treatment and why. This makes the choice among available medicines complicated and uncertain.

One of things that IMI is particularly proud of is the progress we’ve made in the reclassification of subtypes of disease, which means redefining diseases based on their biology and not just symptoms. It’s an extremely scientifically complex area, and we’re steadily increasing the level of understanding of the molecular drivers in a number of disease areas. This is very relevant because it allows for the stratification of patients, and being able to divide patients into meaningful categories is the first step towards tailored treatments for individual patients; it can also help figure out the genesis of these diseases and allow us to intervene earlier before irreparable damage has occurred.

 

 

IMI has funded a series of projects like BTCURE, RTCURE and PRECISESADS where a lot of the work has to do with drilling down into the subtypes of the disease and coming up with biomarkers that more easily allow patients to be stratified into groups. These biomarkers are available to anyone who wants to look at the pathways involved and understand even more about the nature of the disease. They can be used by pharma as more precise indication of the ‘types’ of patients with, say, rheumatoid arthritis, to be considered as inclusion criteria in the design of new clinical trials. In some cases these biomarkers can also be followed as indicators of clinical response to treatment. Once again, it’s a very pre-competitive area, and a public-private partnership is suited to this.

In the case of the new project 3TR, academics will have access to 50 000 high-quality patient samples from clinical trials carried out by pharma companies, covering lupus, rheumatoid arthritis (RA), multiple sclerosis, ulcerative colitis, Crohn’s disease, asthma, and chronic obstructive pulmonary disease, diseases with common or related molecular patterns. Researchers will be able to very carefully decipher the molecular profiles of patients and examine how they responded - or not - to a particular intervention.

Reducing patient burden in clinical trials

Advances in remote assessment will really push progress in this field. This tech convergence is a trend, and we will see more and more sophisticated remote monitoring which will change the game in clinical trials, the potential for which is currently being studied by TRIALS@HOME. Take, for example, somebody with arthritis who has restricted mobility; fundamental parameters like movement and sleep can be measured continuously and in real time with a wearable device that can monitor 24/7, instead of relying on them to record their movements etc. on paper. That’s the idea behind the new project IDEA-FAST, which will identify, profile and validate digital solutions for the remote assessment of fatigue and sleep disturbances - major causes of poor quality of life - in RA, lupus, Sjögren’s syndrome and inflammatory bowel disease, as well as neurodegenerative disorders.

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