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Non-alcoholic Steatohepatitis (NASH)

Collagen Hybridizing Peptides Allow for Quantification of NASH Disease Activity

Introduction

Non-alcoholic Steatohepatitis (NASH) is a nonalcoholic fatty liver disease (NAFLD) in which inflammation and liver damage accompany fat accumulation. NASH is a disease defined by its high heterogeneity: NASH progression is not linear between stages, patients, nor endpoints, complicating clinical trial design and disease management. Collagen Hybridizing Peptides (CHPs) bind to damaged & remodeling collagen, a direct indicator of fibrotic activity, to enable researchers to overcome challenges posed by NASH.

Disease Monitoring

Most antifibrotic drugs primarily pause or slow fibrosis. CHPs can effectively monitor these changes by binding to damaged collagen, allowing real-time assessment of drug efficacy and disease progression.

Clinical Trial Design

Patients with fibrotic conditions can transition between active, stable, and regressive disease states, complicating patient selection for clincial trials. CHPs can stratify patients based on the activity of their disease, enabling efficient clinical trials. It is also unclear whether non-active fibrosis can be treated; distinguishing active from non-active fibrosis serves to improve patient treatability and treatment timelines.

Citations

Nishi, Kotaro, et al. "A thioacetamide-induced liver fibrosis model for pre-clinical studies in microminipig." Scientific Reports 13.1 (2023): 14996.

Reißing, Johanna, et al. "Th2 cell activation in chronic liver disease is driven by local IL33 and contributes to IL13-dependent fibrogenesis." Cellular and Molecular Gastroenterology and Hepatology 17.4 (2024): 517-538.

Kimura, Takefumi, et al. "Thrombospondin 2 is a key determinant of fibrogenesis in non‐alcoholic fatty liver disease." Liver International 44.2 (2024): 483-496.

Liao, Xiaomin, et al. "LncRNA-Gm9866 promotes liver fibrosis by activating TGFβ/Smad signaling via targeting Fam98b." Journal of Translational Medicine 21.1 (2023): 778.

Jaramillo, Catalina, et al. "Quantitative liver fibrosis using collagen hybridizing peptide to predict native liver survival in biliary atresia: a pilot study." Journal of Pediatric Gastroenterology and Nutrition 70.1 (2020): 87-92.

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