Unraveling the mystery of autoimmune diseases

31.07.2020- rheumatism, lupus or multiple sclerosis: autoimmune diseases are very different at first glance. Just like the many projects set up by the public-private partnership "innovative medicines initiative" (IMI) to get to the bottom of them with the combined expertise of pharmaceutical and public research. But instead of looking at the obvious differences, scientists are increasingly focusing on the commonalities: the aim is to find patterns – in order to be able to better categorize and treat patients’ suffering.

Info box: Innovative Medicines Initiative

"we like to think of the immune system as the body’s control mechanism, standing guard – ready to eradicate and eliminate anything that is dangerous," explains pierre meulien, managing director of IMI (s. info box). "but for many people, it doesn’t work that way; misguided, the immune system can wreak havoc."rheumatoid arthritis, for example, attacks the inner lining of the joints, resulting in an inflammation.

millions of europeans are affected by autoimmune diseases, according to meulien – the cost to healthcare systems is estimated to be "over a hundred billion euros a year". A lot has changed. Multiple sclerosis? Before the 1990s, a quasi-guarantee for severe disabilities. Today: increasingly treatable. Rheumatic diseases? A wheelchair was often indispensable. In the meantime, many of those affected can lead a largely normal life with the appropriate medication – and some can even participate in high-performance sports (s. Biotech Report 2019).

But this does not apply to all patients. "we are largely in the dark when it comes to why therapies work for some and not others; and what triggers the diseases in the first place," the IMI chief said. "scientists have no way of predicting which patients will respond well to treatment and what the reasons are."For doctors, this makes the decision on which of the available drugs to prescribe "complicated and uncertain," says meulien.

Autoimmune diseases: finding molecular patterns

Good thing IMI exists. Thanks to its research projects, meulien says it has already made some progress in "reclassifying" disease subtypes. That is, to classify the respective diseases not only according to the external symptoms, but also based on the underlying biology. "it’s an extremely complex field scientifically" – but knowledge of the molecular-level drivers that play a role in the diseases continues to grow. "the ability to sort patients into meaningful categories is the first step toward tailored therapies". And it helps to learn more about the development of the diseases – and thus to be able to intervene earlier with medications.

An example: the project PRECISESADS. Several pharmaceutical companies, universities, research and non-profit organizations, government agencies, small and medium-sized enterprises (SMEs) joined forces here from 2014 to 2019. Blood samples from patients with various autoimmune diseases from all over europe were subjected to a detailed analysis. The scientists studied the genome, the totality of proteins and many other biological parameters. In the process, they found patterns that allowed the approximately 2.000 patients into four different groups with similar disease mechanisms at the molecular level – whether they are z.B. Suffering from rheumatism or lupus. "in a further study, we would have to see whether this classification of patients could actually be used to find out which therapy is best for which patient," says dr. Marta E. Alarcon-riquelme, coordinator of the PRECISESADS project.

rheumatic joints

Rheumatism: one of many autoimmune diseases.
Photo:
©istock.Com / SARINYAPINNGAM

A similar research project, which is still quite young, is "3TR": during its term from 2019 to 2026, more than 50.000 patients and seven immune-mediated diseases at once under the microscope – including multiple sclerosis, asthma and the intestinal disease morbus crohn’s. Here, too, researchers assume that molecular patterns can be found across the disease patterns. clinical studies will show whether the lack of response to therapy is due, among other things, to the fact that the patient in question does not belong to the appropriate molecular group for the treatment, according to dr. Alarcon-riquelme.

With precision against rheumatism and co.

The leaders of "rtcure" (2017-2022) – including bristol-myers squibb, glaxosmithkline and pfizer – are focusing on "only" one disease: rheumatoid arthritis (RA). They hope to understand the underlying causes and mechanisms so well that it will be possible to find people who do not yet have RA – but who are at high risk of developing the disease. The goal is to identify specific patterns ("biomarkers") and understand how they relate to disease development. Ultimately, this knowledge should boost drug research – in the sense of innovative therapies that can prevent the disease or stop it from progressing.

The patterns and biomarkers that scientists are uncovering in projects like PRECISESADS should be available to anyone who wants to study the nature of the diseases in depth. For example, the pharmaceutical industry can use the classification of patients into certain groups for inclusion criteria in clinical studies, says IMI head meulien.

Autoimmune diseases: unexplored territories

There is still a lot of research to be done in the field of autoimmune diseases: this is also shown by a look at the IMI website. Using the search mask on imi.Europe.Eu and enters "autoimmune diseases" and "ongoing," it displays eight very different projects on which numerous scientists are working in public-private partnership. The target z.B. From BIOMAP (2019-2024), on which u.A. pharmaceutical companies such as boehringer ingelheim and pfizer, is to better understand the disease mechanisms behind psoriasis and atopic dermatitis, and ultimately to enable more personalized treatment.

"Research is the best medicine."
photo: ©istock.Com/jevtic

Another project is ULTRA-DD, which recently came to an end in february of this year. It was dedicated to unexplored proteins that could potentially be targets for innovative therapies against autoimmune and inflammatory diseases. "the problem is that a lot of research is needed to find out which proteins make good targets and at the same time are amenable to molecular treatment," IMI newsroom says. "the ULTRA-DD project was set up to make progress in identifying proteins worthy of further investigation". The results of the project are publicly available to researchers. the hope is that this will eventually spur clinical trials for new drugs. As the German association of research-based pharmaceutical companies (vfa) says: "research is the best medicine" – especially if you want to solve a mystery like that of autoimmune diseases.

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Christina Cherry
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