PREDIMID - Development of diagnosis and prognosis tests for Inflammatory bowel disease patient follow-up, especially for Crohn disease: Identification of biomarkers and their validation by SRM (Selected Reaction Monitoring)
The PREDIMID project concerns the identification of biomarkers by proteomics in the context of Inflammatory Bowel Disease (IBD). Crohn disease (CD) and Ulcerative colitis (UC) are both IBD and these patients show lesions within the digestive tract that can severely impact quality of life. The incidences of CD and UC are respectively 10/100000 and 6/100000 per year; whereas IBD prevalence is 0.3% in EU. Life expectancy of IBD patients is close to the one of the general population. A first unmet clinical need for IBD patients concerns lesion diagnosis and stratification of patients according to location and type of lesions. A second issue is the prediction of relapse when the patients are in remission induced by a treatment with biologics (particularly anti-TNF Antibody). Only colonoscopy (invasive, not comfortable and costly) is used as a gold standard to evaluate the presence and severity of lesions or to control for mucosal healing. It has been shown that deep mucosal healing was associated to a lower relapse risk in CD. Beside endoscopy the best marker of relapse in faecal calprotectin which is also a surrogate marker for mucosal healing.
In this context, PREDIMID is a research project involving prospective IBD patients’ enrolment and collection of samples. Proteomic analyses are planned to identify and confirm some potential biomarkers highlighted at the tissue level and at the systemic level (in blood).
Currently, we collect different types of samples: blood-derived products, stools and tissue biopsies, thanks to the clinical activity of Professor Edouard LOUIS (head of PREDIMID) and his colleagues at the University Hospital of Liège, CHU Liège.
We have identified two sets of candidate biomarkers linked to the relapse risk and associated to the patient lesion status by studying CD ulcer, the most frequent CD lesion. The refinement of the two sets of candidate markers and a specific method of quantification are under progress to confirm these biomarkers in blood. Our data should be consolidated thank to the analysis of a second cohort of samples that will be originated from the SPARE clinical trial initiated through the European consortium named BIOCYCLE, project H2020 (https://biocycle-project.eu/).
This validation of markers is mandatory for any commercial development that could be transposed and used in clinics as a companion diagnosis/ prognosis test. Such test could be proposed as an alternative to colonoscopy for IBD patients, if showing the same statistical power and at lower cost. Such laboratory test would have an important impact on the comfort and safety of clinical IBD patient management, on health care related costs and for a company that would develop such a companion test.
Contact Laboratory of Translational Gastroenterology - Marie-Alice Meuwis
AMD - New therapeutic targets for age-related macular degeneration
Age-related macular degeneration (AMD) is the leading cause of blindness in people over 50 in developed countries. Current treatments only help to stabilize the disease. Additionally, resistance to these treatments appears inevitably leading to the irreversible loss of vision. It is therefore crucial to identify new therapeutic targets and develop tools to block them. We have identified a new potential therapeutic target whose expression has been correlated with increased neovascularization typical of AMD. Antibodies blocking this target have been produced in close collaboration with the biotechnology department of the CER group. Two types of antibodies have been produced: Single Chain Fragment Variable (scFv) generated by phage display technique and IgG antibodies produced by mouse immunization. Antibodies are selected through activity tests and in vitro functional assays. In order to test their therapeutic efficacy in a preclinical model, a new equipment adapted to rodents has been acquired and calibrated to induce the laser choroidal neovascularization accurately and reproducibly.
Contact Laboratory of Biology of Tumour and Development - Cassandre Yip
KIT QUANTA - Absolute quantification of proteins in complex matrices (blood, urine and cerebrospinal fluid or CSF) thanks to a “universal” standardization kit
In the world of biomarker discovery, there are few validations of biomarker candidates. The discovery and validation steps in the development of biomarkers remain quite challenging and lengthy. The need for high-throughput technique is therefore urgent. SRM method (Selected Reaction Monitoring) can solve the problem in offering high-throughput analyses. The difficulty of this method lies in the implementation of standardization for absolute quantification. Different standardization approaches now exist in proteomics but all have their limitations. One example is the use of isotopically-labelled peptides for the absolute quantification of proteins. This method is highly specific of the protein to quantify but does not take into account all the bias introduced at each step of the process needed before SRM analyses. In combination with this already well-known technique, our “kit” will allow to control the whole preparation process and therefore will be a useful and necessary tool for longitudinal studies or studies involving a large number of samples in the process of biomarker discovery or validation. Several actors work in collaboration to reach this goal: the Mass Spectrometry Laboratory (MSLab) in ULiège, the laboratory of Proteomics and Microbiology (ProtMic) in UMons and Eurogentec S.A.
Contact Mass Spectrometry Laboratory - France Baumans