Discovery of biomarkers capable of predicting treatment success – Heilpraxis

Intestinal inflammation: biomarkers can predict therapy success

Hundreds of thousands of people in Germany suffer from chronic diseases intestinal inflammation. These diseases are associated with severe symptoms such as chronic diarrhea, fever and pain. Researchers now report that they biomarkers found the clue on the therapy success can give.

As the Federal Ministry of Education and Research on its website reports, around 400,000 people in Germany suffer from inflammatory bowel disease. An international team led by researchers from the PMI Center of Excellence (Cluster of Excellence in Precision Medicine for Chronic Inflammatory Diseases) has just found biomarkers that can predict the success of a biological therapy. The results of the study were published in the journal “Genome medicine“published.

Severely impaired quality of life

As in a stream Message of the PMI Pole of Excellence, in chronic inflammatory bowel infections (IBD) such as Crohn’s disease and ulcerative colitis, a disrupted immune response leads to inflammation of the gastrointestinal tract, which again and again manifests as thrusts.

People with IBD suffer from symptoms such as chronic diarrhea, fever and pain and their quality of life is seriously impaired.

An established treatment for IBD is therapy with antibodies that bind to inflammatory messengers in the immune system bind and thus block their function. The group of these so-called biologics also includes anti-TNF-alpha (anti-TNF-alpha) antibodies.

But about 40% of patients do not respond to this Biological therapies on. Serious side effects can also occur.

Scientists at the PMI center of excellence have now found molecular biology markers that can be used to identify at the start of treatment whether the Anti-TNF Alpha Therapy will knock.

Treatment has not been successful in some patients

For their studies, the teams led by Professor Philip Rosenstiel, Director of the Institute for Clinical Molecular Biology (IKMB) at the University of Kiel (CAU) and Professor Stefan Schreiber, Director of the Clinic for Internal Medicine I of the University Hospital Schleswig-Holstein ( UKSH ) and the IKMB, the blood of people with IBD who have a anti-TNF-alpha antibodies were treated, before the start of treatment and at different times after the start of treatment.

On the one hand, they used the latest sequencing and analysis methods to examine gene expression, i.e. which genes were active in the cells and to what extent, and on the other hand the DNA methylation – this is a chemical modification of genetic material, which also occurs effects on the activities of the genes and generally persists longer.

“Two weeks into therapy, we could see a clear change in the pattern of the gene expression and methylation, which occurred specifically only in so-called responders, i.e. patients who subsequently responded to therapy”explains the first author of the book, Dr. Neha Mishra, bioinformatician at the IKMB and member of the PMI Excellence Center.

Patients who did not have this pattern at this time also received treatment later without success.

50 genes could be particularly suitable as biomarkers
“We then confirmed the analyzes with the help of a second independent patient cohort – this makes the data obtained particularly reliable.”, says Mishra. The researchers found around 4,000 genes in the responders in their activity have been changed.

In the a clinical application it would be too time-consuming and expensive to analyze the patient’s blood samples for all these genes.

Therefore, scientists have drawn clusters of genes from it, all around 50 geneswhich might be particularly suitable as biomarkers, i.e. values ​​with which response to treatment can be predicted in clinical use.

“Our discoveries are a first step towards a real precision medicine approach in the treatment of patients with IBD. The goal of biomarkers is that in the future physicians will be able to make an individual and molecular decision for targeted therapy.”according to Rosenstiel.

“As a result, patients who are not helped by anti-TNF-alpha therapy may discontinue it early and therefore unnecessarily Side effects avoid them and find a suitable therapy more quickly. It could also save the healthcare system unnecessary costs. »continues Rosenstiel.

Approach already in clinical trials

At the Kiel Center of Excellence for Inflammation Medicine (CCIM) at UKSH, this approach is already in a first phase clinical test. “Patients who are being treated with anti-TNF-alpha antibodies at our institution were recently screened for these patterns of gene activity in a study two weeks after starting treatment”explains PMI spokesperson Professor Stefan Schreiber.

“We discuss the results between the disciplines and decide together whether, given the available data, the treatment should continue timely is and must be continued”says the expert.

“So our patients are already directly benefiting from the latest research results from the PMI Cluster of Excellence. At the same time, in this way, we can search for the new biomarkers in practice and method of analysis optimized so that it can hopefully be used clinically in the future. (ad)