Dr Roswitha Gropp, Klinikum der Universität München; Prof. Matthias Siebeck, Klinikum der Universität München; Michael Föhlinger, Klinikum der Universität München; Dr Pia Palamides, Klinikum der Universität München
Ulcerative colitis (UC) belongs to the chronic inflammatory bowel diseases (IBD) of unknown etiology. Manifestations of the disease are highly variable with regard to the onset of the disease, severity, length of phases of relapse and remission, and response to therapies. In order to get a better understanding of the underlying immunological mechanism, three platforms were developed: HuCID Screen, HuCID Disease Map and HuCID animal model. The HuCID Screen Platform is based on an elaborate panel of surface markers of immune cells, chemokines, cytokines and factors which allow immune profiling leading to the stratification of patients.
The HuCID Screen Platform
- identifies subgroups of patients
- identifies two inflammatory conditions
- identifies biological markers and therapeutic targets.HuCID Disease Map depicts the network of interacting cells during inflammation. It predicts efficacy and mechanistic side effects. The HuCID animal model is based on immune compromised mice reconstituted with peripheral mononuclear cells from UC patients.
The HuCID animal model:
- reflects the immunological background of the donor
- reflects the human disease
- validates efficacy and mechanistic side effects predicted by the HuCID Screen and HuCID Disease Map
- promises higher translatability to future human clinical trials
- is a substitute for non-human primates.
Immunological profiling led to the identification of CD1a as a biological marker to discriminate between UC and non UC donors. In vitro and POC study in the HuCID animal model revealed that CD1a expressing monocytes sense and mediate inflammation and that treatment with anti CD1a antibody resulted in decreased pathological symptoms and a decreased pathological manifestation.
The chronic nature of IBD, leads to a significant and lifelong impact on patients’ lives. Patients suffer from abdominal pain, severe diarrhea, blood loss and progressive loss of peristaltic function. IBD is a disease affecting predominantly young people in full swing of their professional and private lives, and thus impedes their career aspirations, instills social stigma and impairs the quality of life. IBD also presents a heavy burden for society and health systems, as treatment, sick leaves, surgery and hospitalization cause substantial costs for healthcare. An estimated 2.5–3 million people in Europe are affected by IBD, with direct healthcare costs of 4.6–5.6 billion Euros/year, and the incidences rise continuously. Current therapeutics have severe side effects and impair the quality of life. Furthermore, many patients do not respond to treatment and a majority becomes refractory to treatment sooner or later.
Proof of concept in vivo.
PCT patent application filed in 2017
Disease Models & Mechanisms (2016) 9, 985-997
J Transl Med (2017) 15: 265.
CD1a is a diagnostic marker and therapeutic target for Ulcerative Colitis. (1) Immunological Profiling lead to the (2) identification of CD1a as a therapeutic and diagnostic marker enabling (3) treatment of immune compromised mice reconstituted with peripheral mononuclear cells from UC patients. CD1a treated mice showed a normal colon appearance and a decreased pathological manifestation.