Periodic Reporting for period 2 - PROFILE (Innovative training network: Immunoprofile-directed stratification of patients with the autoimmune disorder thrombotic thrombocytopenic purpura) Reporting period: 2017-10-01 to 2019-09-30 Summary of the context and overall objectives of the project Problem The increasing prevalence of autoimmune disease represents a major challenge for the healthcare system in Europe. Current treatments are far from being optimal as virtually all patients receive the same, non-specific treatment. In the current PROFILE project, we study the autoimmune disorder acquired thrombotic thrombocytopenic purpura (aTTP). The unmet clinical needs are fine-tuned diagnostic tools and truly personalised treatment options. We want to identify how patients with aTTP match or differ from each other. Specific markers in each patient will be identified which will lead to a barcode profile. Patient stratification by barcode should allow better prediction of relapse. On top of that, treatment options will be identified and developed for each patient group. Impact to societyThe PROFILE project will result in improved diagnosis and treatment of patients suffering from aTTP. This will lead to an increased quality of life and a significant reduction in healthcare costs. Importantly, the strategy applied in this project to aTTP patients can easily be translated to many other autoimmune disease settings.Overall objectivesObjective 1: To understand the role of specific markers (immunoprofiling markers: antibodies and T-cells) in the autoimmune disease aTTPObjective 2: To group patients with matching markersObjective 3: To link the markers with disease prognosisObjective 4: To develop novel treatment strategiesTo reach these objectives, the six early stage researchers (ESRs) working in the PROFILE project are receiving specialized training. They learn how to identify a clinical need, perform translational research, transfer technology and knowledge to the industry, manage intellectual property rights and act as competent managers.The scientific objectives and the high-level training and supervision of the ESRs is realised by the combination of highly skilled and specialized immunoprofiling experts from small and medium enterprises (Icosagen and Protobios, Estonia; Immudex, Denmark; Biokit, Spain; PharmaTarget, The Netherlands) as well as world-leading experts on acquired TTP from academia (KU Leuven, Belgium; Sanquin, The Netherlands; Assistance Publique-Hopitaux de Paris, France). Translational aspects are well covered by the inclusion of expert clinicians (Assistance Publique-Hospitaux de Paris, France) as well as representatives from patient groups (Stichting Zeldzame Bloedziekten, The Netherlands). Specific aspects of the training program are brought to the ESR during network wide events that are organised every 6 months. Importantly, these training sessions are open to all interested and are announced well in advance via our website (www.itn-profile.eu).Dissemination of results emanating from the PROFILE consortium to patients, clinicians and other groups of interest is ensured by the inclusion of the European Hematology Association (EHA) as a partner organisation. Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far Objective 1: To understand the role of specific markers (immunoprofiling markers: antibodies and T-cells) in the autoimmune disease aTTPESR1 and ESR2 succeeded in identifying specific markers (antibodies and T-cell markers) for patients suffering from aTTP.Objective 2: To group patients with matching markersESR2, ESR3 and ESR4 identified and used T-cell peptides, antibody epitopes and anti-idiotypic antibodies to group patients with matching markers. They are developing diagnostic assays which will allow to identify these markers in clinical laboratories all over the world.Objective 3: To link the markers with disease prognosisESR3, ESR4 and ESR6 will work on this objective in the second half of the project.Objective 4: To develop novel treatment strategiesESR5 developed novel ADAMTS13 variants as a novel treatment for aTTP. ESR6 is developing small compounds as a novel treatment for aTTP and ESR2 anti-idiotypic antibodies. ESR2, ESR5 end ESR6 will test the in vivo effect of the novel treatment strategies in the second half of the project. Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far) At the end of the project, we expect to have identified specific markers (T-cell and antibody epitopes) to group patients according to their specific disease characteristics. We will have developed diagnostic assays to identify these markers in clinical laboratories worldwide. Prognostic factors will be identified based on these specific markers, which will improve the follow-up and ‘personal’ treatment of the patients. We will have investigated 3 novel treatment strategies for aTTP.We will have trained 6 ESRs to proceed a career both in academia and industry. They will have learned how to identify a clinical need and how to turn this into a diagnostic assay.We disseminate our work via our website (www.itn-profile.eu) and social media (twitter @ITN_PROFILE), ResearchGate, LinkedIn). We already organized multiple workshops for the general public and an Entrepreneurial Innovation Bootcamp in Rare Diseases. We use the Cordis Channel for dissemination. We disseminate events within PROFILE via the Answering TTP Foundation (Canada), the Rare Disease Organisation (Belgium) and the Stichting Zeldzame Bloedziekten (Nederland). Additionally, a clear and concise informative visual comic will be developed to increase the awareness of clinicians treating patients with (rare) haematological diseases. PROFILE logo PROFILE ESR @ EIBRD2017
