Oral encapsulated transforming growth factor β1 reduces endogenous levels: Effect on inflammatory bowel disease

BACKGROUND: is a combination of the key regulatory cytokine transforming growth factor beta (TGFβ) and all trans retinoic acid (ATRA) microencapsulated for oral delivery to immune structures of the gut. It is in development as a novel treatment for inflammatory bowel disease (IBD). AIM: To measure TGFβ levels in blood and tissue after oral administration of encapsulated TGFβ. METHODS: Animals were orally administered encapsulated TGFβ by gavage. Levels of drug substance in blood and in gut tissues at various times after administration were measured by ELISA. When tested in the SCID mouse CD4+CD25- adoptive cell transfer (ACT) model of IBD, oral TPX6001 alone provided only a transient benefit in terms of reduced weight loss. CONCLUSION: These observations suggest a negative feedback mechanism in the gut whereby local delivery of TGFβ results in reduced local and systemic levels of the active form of TGFβ. Our findings suggest potential clinical implications for use of encapsulated TGFβ, perhaps in the context of IBD and/or other instances of fibrosis and/or pathological TGFβ signaling.