Crohn’s disease is a relapsing, transmural inflammatory disease of the gastrointestinal mucosa that can affect all parts of the intestinal tract as well as extra-intestinal organs. Crohn’s disease affects between 400,000 and 600,000 people in North America. Current estimates for Northern Europe have ranged from 27–48 people per 100,000.
Although the exact etiology remains unknown, the occurrence of Crohn’s disease is strongly associated with mutations of a receptor for microbial pathogens (nucleotide-binding oligomerization domain containing protein 2, NOD2) that recognizes microbial pathogens leading to increased activation of antigen presenting cells. As a result of this altered balance of immune homeostasis, exposure to commensal bacterial antigens causes increased stimulation and proliferation of mucosal T-lymphocytes, leading to inflammatory responses.
The pharmacological management of Crohn’s disease is based on the control of the inflammatory process. Current treatment regimens include:
- anti-inflammatory drugs (e.g. corticosteroids, aminosalicylates), which are the first-line treatment to induce remission in acute active disease;
- immunosuppressants such as azathioprine, 6-mercaptopurine and methotrexate (Feagan, 2000) which are used to maintain remission or treating chronic active disease; biologic immunotherapies (e.g. anti-TNF mAbs including infliximab and adalimumab) which are used to induce and maintain remission.
Tiziana’s intends to administer Foralumab to the small and large intestine via an enteric-coated capsule formulation. Foralumab binds locally to dendritic cells (antigen-presenting cells) lining the GI tract, inducing regulatory T cells supporting immunomodulation locally as well as systemically.