Health & Medicine︱Jørgen Jahnsen PRINCIPLES OF PHOTOPHERESIS Individuals with Crohn’s Disease often suffer from abdominal pain caused by One promising technology for inflammation of the digestive tract. the treatment of T-cell-mediated diseases, such as Crohn’s disease, is extracorporeal photopheresis (ECP) technology. Indeed, a previous A novel therapy could publication in 2015 reported positive results from using ECP in patients with Crohn’s disease. The process of photopheresis starts by withdrawing help patients with blood from the patient. Next, the white blood cells are separated from the red blood cells. These white blood cells are treated with a chemical which active Crohn’s disease makes them photosensitive, before being exposed to UV irradiation. Once they have been irradiated, the cells are EVIDENCE FROM is also a reduced risk of carcinogenesis Professor Jørgen Jahnsen and nflammatory bowel disease (IBD) The symptoms may be constant returned to the patient. PRECLINICAL TRIALS (cancer formation) and an increased PhD student Kristian Espeland occurs in two main forms: Crohn’s or may flare up during episodic Prof Jahnsen and his team have already likelihood that the therapy will induce an of Akershus University Idisease (CD) and ulcerative colitis. events. There is also a risk of further The exact mechanisms by which this undertaken preclinical trials to support anti-Crohn’s disease immune response. Hospital and University of Both types of inflammatory bowel complications requiring surgery, such as process is clinically effective is not yet this new project. The findings of these Oslo are responsible for a disease are chronic, immune-mediated the development of intestinal strictures fully understood. It is thought that trials suggest that hyperproliferative Blue light has been demonstrated to be new clinical trial which aims diseases affecting the gastrointestinal and fistulae. the photosensitisation agent induces T-cells produce about 15-fold more more efficient than other wavelengths at to improve symptoms and tract, particularly the bowel. T-cells to become apoptotic, or self- Gliolan-induced PpIX than normal inducing apoptosis in T-cells, and ECP control the inflammation of The Harvey Bradshaw Index (HBI) is destructing. These dying cells are taken T-cells, meaning that they are selectively appears to be well tolerated and have Crohn’s disease using Gliolan The exact cause of Crohn’s disease is often used to quantify disease activity up by other cells in the immune system destroyed after light irradiation, leaving fewer side effects than traditionally used medication in combination with unknown, but there are several factors in CD based on symptoms and clinical and, along with the chemicals released normal immune cells undamaged. There immunosuppressants. Furthermore, blue-light photopheresis. This hypothesised to be involved, including signs and includes five factors: number as a result of the process, increase the approach will selectively cause genes, autoimmune responses to the of loose bowel movements, degree activity of regulatory immune cells. the death of pro-inflammatory body’s tissues, previous gastrointestinal of abdominal pain, general well- Ultimately, ECP seems to dampen down One promising technology for the cells which contribute to the infections or an imbalance in the gut being, presence of abdominal mass, inflammation without lowering the inflammatory bowel disease, bacteria. The underlying pathology of and complications. In addition to body’s immunity against other infections, treatment of T-cell-mediated diseases, whilst showing minimal short- Crohn’s disease is a T-cell-mediated assessing disease activity indices, the resulting in better long-term outcomes and long-term side effects. such as Crohn’s disease, is extracorporeal response (T-cells are important for bowel inflammation can be evaluated for patients. the activation of immune cells), by endoscopic examination and/ photopheresis (ECP) technology. characterised by an overproduction or measuring objective markers of However, a major disadvantage of of pro-inflammatory components, i.e. inflammation such as faecal calprotectin this approach is that it kills both Exogenous activated hyperproliferative T-cells. The and C-reactive protein. diseased and normal cells after UV 5-ALA effects of these pro-inflammatory cells light exposure. Thus, there is an urgent may overpower the anti- The current goal of treatment is to need for a non-toxic, selective and more inflammatory effects induce and maintain remission whilst effective alternative. of other immune minimising side effects from the drugs 5-ALA cells with regulatory and allowing time for the tissue in One such alternative, which will be function, leading the gut to heal. This is most often used by the investigators, is a two-step Glycine to uncontrolled achieved using immunosuppressive process called BLUE-PIT. This process + 5-ALA Porphobilinogen inflammation and/or biological drugs, but these uses a drug called Gliolan, which is Succinyl CoA and gut symptoms. are not effective in all patients. often employed to visualise tumours PSG deaminase Heme Furthermore, there are risks involved prior to surgery as it causes them to Uroporphyrinogen ||| MANAGEMENT OF with long-term use of these medications. glow fluorescent red. Gliolan leads to Ferrochelatase CROHN’S DISEASE Therefore, there is an urgent need the accumulation of protoporphyrin Symptoms vary to develop alternative therapies for IX (PpIX), a potent photosensitizer, in Protoporphyrin |X dramatically between CD, particularly for patients who are hyperproliferative cells, such as the individuals and usually dependent on steroids, or who have activated T-cells in Crohn’s disease. Coproparphyrinogen ||| start in childhood or a disease which is nonresponsive to Blue light (405 nm) is the most effective Protoporphyrinogen |X early adulthood, but available treatments. wavelength for PpIX activation which generally consist of consequently induces apoptosis, mainly diarrhoea, abdominal Professor Jørgen Jahnsen and Kristian in activated T-cells. The treated cells pain, bleeding and weight Espeland of Akershus University Hospital are transferred back to the patient loss due to malabsorption of and the University of Oslo are hoping to and can induce further, secondary Exogenous 5-ALA leads to accumulation of protoporphyrin-IX through the heme biosynthesis nutrients and decreased appetite. provide one such therapy. immune responses. pathway. 1 www.researchoutreach.org www.researchoutreach.org 2 BUFFY COAT LINE in combination with blue light SALINE LINE photopheresis in patients with active Crohn’s disease. All patients will Behind the Research undergo treatment every two weeks for ten weeks with evaluation at week 13. If IRRADIATION BAG any effect is observed during week 13, the study is eligible for an extension for Dr Jørgen Dr Kristian up to 12 months. Jahnsen Espeland Primary endpoints include clinical response as measured by a reduction of three or more points in HBI score. E: [email protected] T: +47 6796 6013 W: www.ahus.no W: www.uio.no This reduction in symptom score must ideally be sustained after treatment. PUMP SEGMENT Safety and tolerability will be monitored Research Objectives through frequency, seriousness and Prof Jahnsen and PhD student Espeland conduct a clinical trial on Gliolan medication in combination with blue-light intensity of adverse events. photopheresis in patients with active Crohn’s disease. 0,20µ FILTER Secondary endpoints include endoscopic improvement, quality of Detail life questionnaires, faecal calprotectin, C-reactive protein, and mechanisms of Jørgen Jahnsen research experience in the field of Collaborators action (differences in T-cells and other Oslo universitetssykehus HF gastroenterology. National Coordinator Qian Peng (Professor, MD, PhD), cells before and after treatment). The Postboks 4950 Nydalen (NC) of several phase II/III clinical trials. Eidi Christensen (Associate Professor, researchers will also be looking for 0424 Oslo Principal Investigator (PI) on the project. MD, PhD), Astrid Aandahl (MD), clinical remission throughout the study. Norway Andreas Ulvær, Kristian Espeland (MD, Kristian Espeland is a PhD candidate PhD student), Sagar Darvekar (PhD), The overall aim of the study is to Bio at the University of Oslo and Sponsor Andrius Kleinauskas (PhD candidate), RECIRCULATION BAG investigate whether this kind of Jørgen Jahnsen is professor of Principal Investigator (SPI) on the project. Morten Oksvold (PhD), Trond Warloe medicine and gastroenterology and (MD, PhD), Petras Juzenas (PhD), Vlada photopheresis is safe and presents an holds a PhD on bone metabolism and Vasovic (PhD) option for a larger randomised Funding body composition in inflammatory South-Eastern Norway Regional controlled trial in the future. In addition, bowel disease (IBD). He has broad Health Authority Prof Jahnsen and his team will consider whether photopheresis provides CONNECTOR PORT potential therapeutic benefits for other INJECTION PORT CE 0051 diseases, such as other T-cell-mediated References Personal Response diseases or patients already receiving The research team employs two-step photopheresis to separate white blood cells from red blood cells and consequently treat the former with Gliolan and blue light. photopheresis as a treatment. Jahnsen, J., Espeland, K. et al. (2019). Extracorporeal What is the most promising result so far? photopheresis of patients with Crohn’s disease It is far too early