Stelic Institute & Co.

Fibrogenesis Project: Science

Stelic’s scientists have identified a set of novel functional molecules, in what we term “G family” that modifies AS niche cells, as a novel therapeutic target for a treatment of fibrogenesis.

“G family” targets are up-regulated in various fibro-proliferative disease models as well as patient samples. Inflammatory cells mainly produce G family proteins in response to certain stimuli. Functionally, G family molecules are involved in “trans-stromal” migration of leukocytes, a final step for trans-endothelial migration from the bloodstream. According to an extensive series of in vivo siRNA gene-silencing studies in various disease models, G family molecules, #1 to #10 have been characterized targets involved in liver cirrhosis, NASH (non-alcoholic steatohepatitis), pulmonary fibrosis, renal fibrosis, intestinal fibrosis including Crohn’s disease stricture, pancreatic fibrosis, skin fibrosis, cardiomyopathy, diabetic retinopathy or Neurodegenerative disease (Figure 1). G family inhibitors would be novel anti-fibrotic drugs with regeneration-promoting efficacy (Figure 2).

(Figure 1)

Fibrosis represents the final common pathway of virtually all chronic diseases in various organs. Current treatments for fibrosis are limited to removing the causing agents, but host fibrotic healing responses [“fibrogenesis”] progress irrespective of their causes. Organ replacement is the only effective treatment for end-stage fibrosis at present. It is still a challenge to develop anti-fibrotic agents.

Fibrogenesis is a dynamic, on-going host response, since host-derived inflammatory cells create local fibrotic fields [“pathological niche”] (Figure 1). Long-term retention of activated macrophages and fibroblasts within pathological niche maintains intricate networks of various inflammatory and fibrotic mediators that overcome host fibrolytic responses. Stelic’s novel therapeutic strategy is to shutdown malignant cycle of fibrogenesis within the pathological niche by inhibiting persistent accumulation of activated macrophages and/or fibroblasts.

Figure2