Project oraCle - New integrated approach to the oral therapy of Crohn’s Disease
POR-FESR 2014-2020,  Autonomous Region Friuli Venezia Giulia
Activity 1.3.b.

20 months, from April 2017 to December 2018

Principal investigators for DI4A Department
dott. Emanuele De Paoli and prof. Mauro Spanghero

Crohn’s Disease (CD) is an idiopathic autoimmune disease of the digestive tract that mainly affects the ileum and colon. Symptoms (abdominal pain, diarrhoea, weight loss, flu-like syndrome) and complications, both intestinal and extraintestinal, have a serious impact on the life quality of patients, who are mostly young (10-25 years). The rate of incidence, ranging from 150 to 200 cases per 200,000 people, is unfortunately growing, especially in patients of pediatric age. To date, classical corticosteroid treatments are not able to alter the evolution of the disease, but can only control  the inflammatory state. Only monoclonal antibody therapy against TNF alpha has been able to revolutionize the patients’ lives, giving them however severe side effects.
The aim of the oraCle project is to create a therapy that carries the anti-TNF alpha antibodies directly to the intestine, both avoiding patient’s immunosuppression caused by the systemic exposure and maintaining its therapeutic efficacy.
Transactiva Srl, a biotech company specialized inmolecular farmingof therapeutic proteins in plants, intends to produce the anti-TNF alpha antibody in rice seeds. The purified protein will be used in combination with the probiotic Kluyveromyces marxianus fragilis (TURVAL B0399) produced by Turval Laboratories S.r.l. to develope an innovative oral therapy. Recent studies demonstrate that probiotics improve the digestive functions, the treatment and the prevention of recurrences in people with irritable bowel syndrome. The choice of gastroresistant capsules and excipients, essential elements for the protection of the active substances and their controlled release into the intestine, will be carried out by Biofarma S.p.a., a leader in the production of food supplements, medical devices and cosmetics. The University of Udine will evaluate the antibody’s bioactivity, protected by different matrixes, to the chemical, enzymatic and microbiological treatments using in vitro models of the digestive system, while the therapeutic efficacy will be evaluated in vivo by the University of Trieste thanks to an animal model that mimics Crohn’s disease. Further commitments of the project are the optimization of the genetic transformation techniques of the plant bioreactor and the improvement of out-of-soil cultivation techniques (University of Udine).

Project partners
- Transactiva S.r.l.
- Biofarma S.p.a.
- Turval Laboratories Srl
- University of Trieste
- University of Udine

Working group
Prof. Mauro Spanghero, Dr. Carla Fabro, Dr. Chiara Sarnataro, Dr. Eleonora Gulisano

For more information