Transforming growth factor beta (TGF-β) is a cytokine with powerful immunoregulatory and anti-inflammatory properties. Its role in the pathogenesis and treatment of inflammatory bowel disorders (IBD), such as Crohn's disease and ulcerative colitis, has been a subject of significant scientific investigation. In patients with IBD, dysregulation of TGF-β signaling has been observed, particularly due to overexpression of SMAD7, an intracellular inhibitor of TGF-β signaling. This impairment results in reduced anti-inflammatory activity, contributing to the persistent inflammation characteristic of IBD.

Several preclinical studies and early clinical trials have explored therapeutic strategies aimed at restoring TGF-β signaling. The most notable approach has been the use of antisense oligonucleotides targeting SMAD7 (such as mongersen), which indirectly enhance TGF-β activity. Early phase trials with mongersen showed promising results, with improved clinical remission rates in patients with Crohn’s disease. However, larger phase III trials did not confirm these benefits, and some studies were halted due to lack of efficacy.

Direct administration of TGF-β itself as a drug is not currently practiced due to concerns about systemic side effects, including fibrosis and carcinogenesis. Nonetheless, the modulation of TGF-β pathways remains a scientifically validated target in IBD research, and ongoing studies continue to investigate more targeted approaches. Thus, while scientific rationale and some clinical evidence exist, limitations in efficacy and safety have thus far prevented widespread therapeutic adoption.