Lay Summary
Proposal No. IBD-0088
Principal Investigator: Maria-Anna Ortner, M.D.
Applicant Organization: Hospitalier Universitaire Vaudois (Lausanne, Switzerland)
Project Title: Photodynamic therapy in Crohn's disease
Period of Award: February 1, 2004 – June 30, 2006
Crohn’s disease is a chronic inflammation that can affect any part of the gastrointestinal tract. Furthermore, it is frequently associated with systemic manifestations (skin, joints, eyes). Inflammation may result from an inappropriate immune reactivity to the bacterial flora of the intestine of individuals who are genetically susceptible. The inflammation is a consequence of an irreversible imbalance favoring a pro-inflammatory over a protective anti-inflammatory immune response. Since the incidence and prevalence of Crohn’s disease are rising, the effect of this disorder on health spending is considerable.
Therapy of Crohn’s disease is aimed at modulating the immune system; alternatively, they may suppress and/or alter the bacterial microflora of the gut. Patients must still rely on multiple medications to control their disease and the effectiveness of drugs is limited by treatment related toxicity.
The aim of our study is to evaluate photodynamic therapy (PDT) in Crohn’s disease. At the moment, PDT is primarily used to treat tumors, but it is a promising new approach in immunological diseases as well. Psoriasis and rheumatoid arthritis, diseases with an immune mechanism similar to Crohn’s disease, have been successfully and safely treated with PDT, which requires drugs, called photosensitizers. They are non-toxic in the dark. After being activated by light, a photochemical reaction occurs. It leads to killing of cells, such as, activated immune cells. Furthermore, PDT can inactivate several microbial strains. Since bacteria play a role in the induction and perpetuation of intestinal inflammation in Crohn’s disease, this effect of PDT is desirable. Thus, PDT could be the first treatment option with an effect on both immune system and intestinal bacterial flora.
The purpose of this proposal is to evaluate the effect of PDT on the healing of colitis and the safety of treatment. In addition, the optimal drug dose, light dose, and modality of illumination will be identified. Finally, the basic mechanisms of modifying the immuno-inflammatory response and the intestinal bacterial flora will be investigated. These questions will be evaluated in standard cell lines, human lymphocytes from Crohn’s patients as well as healthy subjects and different mouse models of inflammatory bowel disease. The information gained could lead to a new therapeutic approach with a favorable side effect profile. If this project yields positive results, a prospective study in patients with Crohn’s disease is planned. The expected outcome is control of colitis and healing of the intestinal mucosa.