An estimated 3 million people in Europe, mostly adolescents and young adults, have been diagnosed with inflammatory bowel diseases, which are chronic disorders of the gastrointestinal (GI) tract caused by immune reactions. Symptoms include diarrhea, fatigue and abdominal pain. In severe cases, IBD may result in bowel perforation, severe bleeding, colorectal dysplasia and cancer.

The New Deal project is exploring whether a biological therapy using an RNA interference (RNAi) mechanism and small interfering RNA (siRNA) molecules can improve the therapeutic efficacy and safety of IBD treatment through the specific inhibition of two janus kinases (JAK1 and JAK3) by the means of specific siRNAs. RNAi mechanisms and siRNA have been shown to prevent the expression of targeted genes in humans. These JAKs control the signalling pathways of several cytokines and have been recently identified as potent molecular targets in IBD clinical trials. The siRNAs used in the project and orally administered are expected to allow specific targeting of the inflamed gut thanks to a combination of innovative nanostructured lipid carriers embedded in smartly designed polymer capsules developed by the New Deal consortium.

Polymer capsules will protect the siRNA nanotherapeutics along the GI tract, while lipid nanoparticles will enable them to cross mucus, the intestinal wall, the plasma membrane and other barriers of the target cells so the siRNA can be delivered locally.

Conventional IBD therapies, 5-aminosaliycilates (5-ASA) and corticosteroids, are not effective in a large proportion of patients. The emergence of biological therapy, meaning the use of therapeutic antibodies mainly targeting TNFα, still insufficiently treats a significant number of IBD patients and is associated with an increased risk of infections. The New Deal project's treatment will consist of an oral administration of the siRNA medicine locally delivered directly to the inflamed gut.

"The New Deal concept could revolutionize IBD therapies for the great benefit of patients and European health-care systems," said Leti's Fabrice Navarro, coordinator of the project. "In the near future, it could strengthen the competitiveness of European biotech and medtech companies in the fields of RNAi medicines and targeted therapy through innovative delivery technologies."

Leti researchers in the four-year, €6 million project will design nanostructured lipid carriers for the in vivo delivery of siRNA across the gut's mucosal barrier.