Targeted therapeutics for pancreatitis - PubMed
6 hours ago
- #pancreatitis
- #disease modification
- #targeted therapeutics
- Acute pancreatitis (AP) can lead to severe complications like organ failure, necrosis, and death, and may progress to chronic pancreatitis (CP), which involves fibrosis and chronic pain.
- Early therapeutic targets include inhibiting Orai1 (e.g., CM4620/Auxora) to prevent calcium overload and mitochondrial protectants (e.g., NIM811) to reduce cell death.
- For systemic inflammation, targets involve NLRP3 inflammasome, neutrophil extracellular traps, HMGB1 signaling, and ADAM17/TACE cytokine shedding.
- In chronic pancreatitis, treatments focus on pancreatic stellate cells to reduce fibrosis and neuroimmune pain sensitization to manage chronic pain.
- Potential therapies include repurposed drugs (e.g., pirfenidone, tocilizumab), genotype-matched CFTR modulators, and cell-based approaches.
- Clinical trial challenges include timing drug administration to disease stages and using endpoints like organ failure, fibrosis, and pain progression.