A parasite enzyme as a new therapeutic agent in Inflammatory Bowel Diseases – ACROHNEM

The present project (ACROHNEM: Anti CROHN Enzymatic Molecule) aims at the development of a well- characterized parasite protein as a new therapeutic agent in dramatically increasing Inflammatory Bowel Diseases (IBD), with a particular focus on childhood onset Crohn’ s disease(CD).

The increased frequency in immunological disorders, including allergic diseases, autoimmune disorders or inflammatory bowel diseases (IBD), appears associated with recent changes in our environment. The absence of parasitic worms, a situation seen in industrialized world, or the intensive anti-parasitic treatment in some emergent countries, might have disturbed the long- term developed regulatory networks and, at least partly, explain the dramatic increase in inflammatory disorders.This hypothesis is supported by numerous experimental evidence favouring the protective effects of several helminth infections in models of immunological disorders.

Among other helminths, Schistosomes are considered as “masters of regulation” and extensive studies performed in the Project Coordinator group have led to the characterization of one unanimously recognized as the probably best known Schistosome parasite enzyme , now named CA 995. Preliminary studies indicate that the CA 995, combining immuno-regulatory and free radical scavenger properties might represent one of the major factor implied in the down -regulation of intestinal inflammation. In addition, this molecule, produced in recombinant form, has been already successfully used in clinical trials for safety and immunogenicity studies, including in children, representing therefore a highly promising therapeutic anti-inflammatory agent, particularly valuable in inflammatory diseases such as IBD.

The aim of the present project is thus to develop this new potential therapeutic agent from basic research to clinical studies for the treatment of IBD. In the context of a partnership between 1 Biotech company specialised in the development of pre-clinical models for IBD, 2 academic research teams, and one Clinical Investigation Center, three main approaches will be undertaken :

1. to confirm and extend the anti-inflammatory properties of CA 995, in the more relevant animal models for IBD;
2.to develop an advanced drug delivery system for this protein allowing for oral administration and colon targeting;
3. to perform the organ toxicity screening methods required by regulatory authorities before setting – up 2 pilot clinical phases in adult and in children. The latter approach is based on epidemiological studies showing that, during the last twenty years, CD incidence particularly increased in the 10–19-year-old age group.

The expected results of this innovative project are of primary importance, for the demonstration of the anti-inflammatory properties of this unique parasite molecule, and its potential use to prevent or reduce intestinal inflammation in the devastating Crohn’s disease, representing therefore a major breakthrough for the specific control of Inflammatory Bowel diseases, which could be also extended to other inflammatory states including autoimmune diseases.