The field of personalized medicine has evolved rapidly since the introduction of expensive novel targeted biological treatment options for a wide variety of diseases, such as inflammatory diseases and multiple cancer types. However, limitations of current technologies do not allow the visualization of the molecular phenotype or heterogeneity within patients, who often only partially respond to a treatment. Surprisingly, even in the current era, it remains completely unknown whether a drug reaches its actual target in the tissue and if a sufficient local concentration is reached for target engagement to achieve treatment response. Thus, treatment and dose administration are empirical, leading to high costs and delays in finding an effective individualized treatment. These inefficiencies are especially crucial in inflammatory bowel diseases (IBD), ulcerative colitis, and Crohn’s disease. These chronic relapsing inflammatory disorders of the gastrointestinal tract affect 2.5Mio patients in Europe. The majority of newly diagnosed patients are in adolescence or early adulthood and in the midst of their family life, career, and social development. Though luckily not life-threatening, the disease comes with significant morbidity and complex treatment strategies and is associated with a high social burden and medical costs of ~€10 billion annually in the EU. This is due to the unpredictable response to expensive biological immunomodulating therapies and is thereby frustrated by high primary non-response (30-60%) and loss of response over time (48-58%). Liquid biomarkers, tissue markers, gene expression signatures, therapeutic drug monitoring of serum levels, and analyses of the microbiome do not yield an adequate prediction of individual responses or dosing. Thus, burning issues to be solved are: 1. Does the drug reach sufficient concentrations at all inflamed areas to block the target? 2. What is the mechanism of action? 3. Can we stratify patients into the specific therapies? 4. How should we dose individual patients?
We are proposing a technology that aims at combining molecular data to stratify individuals based on their probability to respond to treatment taking inter-patient and intra-patient heterogeneity into account. It will allow a more personalized medical treatment that can predict which patients will respond to certain treatments and what the optimal dosage is, eventually resulting in lower non-response rates. In addition, these results will improve our knowledge of existing biological therapy and enable the development of novel therapeutic targets and faster drug development in collaboration with the pharmaceutical industry. Our technology will enable and provide robust precise measurements, required for precision medicine. In the context of msGUIDE, we will develop a groundbreaking technology that, for the first time, will simultaneously visualize and quantify local drug concentrations throughout the whole colonic mucosa in real-time to gain insight into drug distribution of multiple therapeutic agents. This will be achieved by enhancing HD-White light endoscopy (HD-WLE) performance with concurrent highly sensitive Near-Infrared Fluorescence and Reflectance Multispectral Imaging (NIR-FRMI), using fluorescent labeled drugs employed in IBD treatment.
