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Fibrosis and Inflammation models

Inflammation is part of the body’s defence mechanism, a response to an irritant such as pathogen or chemical substance. Inflammation initiates tissue repair. Fibrosis on the other hand is a process of pathological wound healing. Fibrotic scarring in central organs such as the liver or kidney due to excessive accumulation of extracellular matrix (ECM) leads to distortion of the tissue architecture and ultimately loss of organ function. Severe fibrosis is estimated to account for 45% of deaths in the developed world and treatment options are limited.

Here at Sygnature (formerly under the name RenaSci) we have established a range of in vivo and ex vivo pharmacology models, which enables careful assessment of drug candidates.

 

Examples of our validated and advanced fibrosis models include:

Therapeutic Indication Models Characteristics
Kidney Disease Adriamycin Model (mouse) Focal segmental glomerulosclerosis (FSGS), moderate-severe fibrosis
Anti-GBM Model (mouse and rat) Nephrotoxic nephritis (NTS), inflammation
STZ/HFD Model (mouse and rat) Diabetic nephropathy
ZDF Model (rat) Diabetic nephropathy, inflammation, fibrosis
Liver Disease:

NASH and fibrosis

Choline deficient (CD) model (mouse) Moderate fibrosis with NASH, non-obese without metabolic disease
H-FFC model (mouse) Moderate fibrosis with NASH, hyperglycaemia and overweight
H-FFC ob/ob model (mouse) Moderate fibrosis with NASH, hyperglycaemia, insulin resistance, dyslipidaemia and obesity
H-FFC CCl4 model (mouse) Severe fibrosis with severe NASH, non-obese without metabolic disease

 

The study design elements for assessing novel drug potential include:

 Kidney function and pathology readouts:

  • Kidney histopathology: glomerulosclerosis, tubulo-interstitial inflammation, glomerular fibrosis, tubulo-interstitial fibrosis and more
  • Plasma biomarkers: urea, creatinine, cystatin C, glucose, insulin, HbA1c, glucose tolerance and more
  • Urinary biomarkers: ACR, PCR, creatinine clearance and inulin clearance, urinary glucose excretion, TIM-1, NGAL and more

Liver function and pathology readouts:

  • Liver histopathology: steatosis, hepatic ballooning, lobular inflammation, NAFLD activity scoring (NAS), fibrosis, F4/80, α-SMA and more
  • Liver biochemistry: hydroxyproline, triglyceride, cholesterol, NEFA content and more
  • Plasma biomarkers: TIMP-1, PIIINP, Hyaluronic acid, ELF test, ALT, AST, bilirubin and more

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