Results support the claims that PBI-4050 anti-fibrotic activity could also be used to address various liver conditions such as nonalcoholic steatohepatitis ("NASH"), a condition affecting 2% to 5% of Americans.
PBI-4050's favorable effect in reducing the progression of fibrosis in liver was demonstrated in two different "gold-standard" animal models. The first is a diabetic mouse model in which the animals develop liversteatosis. Similar to what is observed in humans, the untreated animals accumulate fat in the liver causing inflammation and leading to permanent damage and scarring, and reducing the ability for the liver to function properly. Diabetic mice treated with PBI-4050 had a significant reduction of liver lesions and steatosis measured by histology as well as a significant reduction in key biomarkers such as including TGFβ-1, Collagen 1, MMP2 and TIMP-1.
In a second model, the liver fibrosis is induced by chronic administration of carbon tetrachloride (CCL4), a chemical which at high chronic dose, causes irreversible damage to the liver and the kidney. Again animals treated with PBI-4050 displayed a significant reduction of liver lesions as evidenced by histology and relevant biomarkers.
"These results clearly indicates that PBI-4050 anti-fibrotic activity is at the core of the fibrosis regulation pathway affecting multiple organs and tissues", stated Dr. Lyne Gagnon, Head of Biology & Immunology at ProMetic.
Dr. John Moran, a member of ProMetic's Board of Directors stated "Since patients with diabetes are more likely to develop complications affecting the kidneys and liver, the positive effects observed with PBI-4050 in multiple challenging animal models bodes well for its potential use in this patient population."