A potent inhibitor of PAI-1, MDI-2517, mitigates disease severity in a preclinical systemic sclerosis model - PubMed
4 days ago
- #Autoimmunity
- #Therapeutics
- #Fibrosis
- Systemic sclerosis (SSc) is a complex condition characterized by progressive fibrosis in multiple organs.
- PAI-1 is implicated in SSc pathogenesis and is a potential therapeutic target.
- Single-cell and spatial RNA-seq analysis showed elevated PAI-1 in myofibroblasts from SSc patients.
- MDI-2517, a PAI-1 inhibitor, reduced profibrotic markers COL1A1 and ACTA2 in SSc dermal fibroblasts.
- In a preclinical SSc model, MDI-2517 significantly reduced skin and lung fibrosis.
- MDI-2517 was more effective than pirfenidone, mycophenolate mofetil, and tiplaxtinin at lower doses.
- MDI-2517 also attenuated weight loss and reduced key profibrotic markers.
- The findings highlight PAI-1's role in SSc and MDI-2517's therapeutic potential.