Porcupine is a novel drug target that aims to address the issue of high unmet need in fibrosis.
Porcupine is a key enzyme in the WNT signalling pathway. WNT signalling has been implicated in fibrogenesis, and therefore inhibition of WNT signalling is likely to prevent several mechanisms important for fibrotic disease progression.
Anti-inflammatory therapies have limited efficacy in the treatment of fibrosis. Several recent publications have shown that Porcupine (PORCN) inhibitors can be beneficial in the treatment of fibrotic indications, including renal, heart, lung and skin conditions. Our team of scientists have demonstrated efficacy in a mouse unilateral ureteral obstruction (UUO) model of kidney fibrosis with our novel agent. We are also exploring activity of a PORCN inhibitor in models of IPF and NASH/ liver fibrosis.
By targeting this pathway, we aim to prevent progression or reverse fibrosis in patients with these devastating diseases.
Porcupine inhibitors suppress fibrosis in murine model of IPF
Image representative of group mean Ashcroft scores. Scale bar indicates 1.2 mm. Small region of dense collagenous connective tissue (fibrosis; black arrows demarcate) and lymphocyte infiltrates/aggregates (*) are present. A bronchiole (Br) and blood vessels (BV) are indicated.