THE NEW DEAL PROJECT
The NEW DEAL project aims to develop a highly selective and local therapy with an improved efficacy and safety profile for IBD patients. This treatment might be an alternative to the existing therapies.
The use of nanotherapy based on siRNA, targeting specifically the molecular JAK1/JAK3, is a new approach to treat inflammatory bowel diseases. This innovative medicine will deliver a targeted and local therapy directly to the inflamed gut, through the gastrointestinal tract.
Inflammatory bowel diseases (IBDs) affect more than 3 million people in Europe.
Among these IBDs, Crohn’s disease (CD) and ulcerative colitis (UC), which are chronic and immune-mediated disorders of the gastrointestinal tract, affect mainly adolescents and young adults. The patients suffer from symptoms such as diarrhoea or abdominal pain but can also lead to bowel perforation, severe bleeding or cancer.
For now, the conventional IBD therapies can only treat half of the patients with UC but not patients with CD; while the biological therapy can only treat a minority of patients with IBDs because of an immunogenicity and an increasing risk of infection.
The loss of response in current immunotherapies, is becoming an emerging clinical problem. By contrast, JAK inhibition is an excellent molecular target and will greatly improve the clinical response of future IBD therapy.
On top of this, being able to deliver the therapy locally to the inflamed gut would be a real added-value as compared to chemotherapeutics or biotherapeutics that are delivered by parenteral injection, where systemic toxicity and unwanted side effects have been observed.
Inhibitory treatment will be applied locally, thus limiting the extend of JAK3 inhibition.
The gastro-intestinal tract exhibits extreme pH conditions. siRNA-nanotherapeutics are vulnerable in the biological environment which make it difficult to distribute them.
To deal with this difficult environment, the NEW DEAL project will develop smart polymer-based microcapsules to package and protect our siRNA-loaded NCLs and control their release.
The NLCs embedded in the microcapsules will be administrated orally and will transit along the gut intestine tract.
siRNA nanotherapeutics will be released at the intestinal mucosa; the lipid nanoparticles favouring thus the transport of siRNA through the biological barriers from the mucus to the intracellular cytosol compartment.