Periodic Reporting for period 1 - msGUIDE (Insight into Drug Distribution and Local Concentration using Multispectral Imaging of Fluorescent Drugs in Inflammatory Bowel Diseases)
Okres sprawozdawczy: 2022-04-01 do 2023-03-31
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.
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.
The msGUIDE consortium has developed a first endoscopic prototype, which has already been approved for clinical studies. The second msGUIDE prototype with the full versatility is under development. In addition, several spectroscopy systems which complement our novel hybrid endoscope have been prototyped. Further, we have developed a first rigid multiparametric phantom, which was tested during clinical endoscopy procedures. The phantom has also been tested with the spectroscopy system, and currently the readouts are analyzed. The phantoms developed within msGUIDE will help to standardize the endoscopic procedures during patient screening to allow for comparable information and are a prerequisite to bring our novel solution to the clinic. We have also programmed a software to control the msGUIDE prototype, acquire data, and visualize the readouts in real-time, which is currently tested in a clinical study. In parallel, we are designing novel IBD drugs labelled with fluorescent markers. The development and characterization of one labeled drug has been completed and its stability batches are due to be produced in the following months. In the upcoming periods of the project we will assess these labeled drugs in a safety and dose-finding study. As we have already achieved very exciting results in msGUIDE the project team has presented results at several scientific and medical conferences and has reached out to the general public on social media and science fairs.
msGUIDE will enable in vivo real-time imaging of local drug concentrations and distribution in IBD, resulting into faster targeted screening and stratification of patients during drug development and during implementation in clinical practice. This will lead to more efficient drug usage and prescription. The radically new technology developed within msGUIDE will have an enormous positive effect on our economy and society in the long-term. It is estimated that the annual cost of biological therapy per patient is >25.000€, which becomes substantially higher for the non-responsive cases at the primary therapy or for those that lose response over time. Moreover, as a chronic disease with low mortality but high disability rates, IBD does not affect only the healthcare economy. More than 50% of the total social costs of IBD are indirect costs, such as sick leave or early retirement. Therefore, IBD contributes to an ever-increasing burden, not only on health-care systems but also on the economy as a whole . If all these are combined with the exponential increase in the predicted new IBD cases over the next few years, it becomes apparent the huge burden of IBD treatment in the global economy. Consequently, msGUIDE will bring a great relief for patients suffering from IBD but at the same time will help to significantly decrease healthcare costs for the treatment of IBD and social costs related to the disease. msGUIDE is still at its beginning, but taking our very promising results into consideration, we are confident to achieve our aims and will in the next periods approach a detailed business plan to define the next steps to finally bring our technology to the market and into the clinical practice.