Physiogenex’s proprietary and innovative animal models
The nutritional and translational vision
Physiogenex’s ultimate goal is to provide a panel of models for predicting the clinical functional effects of a compound, early in the discovery/preclinical stages of development. Too many experimental models have poor predictive value with respect to human disease, frequently resulting in failed clinical trials and escalating drug development costs.
At Physiogenex, we believe that defining the key mechanisms of metabolic and cardiovascular diseases requires the development of new animal models and associated techniques which help to define the precise mechanism of action of novel compounds.
Poor nutrition is the main factor responsible for obesity, type II diabetes, and cardiovascular diseases in western societies. Western diets include large amounts of saturated fat and fructose in soft drinks1, both of which foster a “cardiometabolic syndrome”.
Lipid, lipoprotein and glucose metabolic disorders are interconnected and cause several human diseases 2 3 4. For example, 2/3 of deaths among diabetic patients are due to cardiovascular disorders. This underlines the importance of being able to measure direct as well as indirect effects of medicines in integrated animal models and/or panels of complementary models of glucose, lipid and lipoprotein disturbances.
While genetic models can provide answers to specific questions, Physiogenex is convinced that the nutritional approach is the best solution for obtaining a thorough pathophysiological picture of the human “cardiometabolic syntrome”. Nevertheless, the two approaches can be combined when needed.
Physiogenex has acquired unique expertise on diets, animal strains, housing/breeding conditions, and technological tools to overcome common bottlenecks:
- managing phenotypic changes according to diet composition, as well as the nature and age of the animal strain,
- selecting homogenous populations in order to improve sensitivity and to provide reproducible and validated data
The following marketed drugs were validated in our models: biguanide, thiazolidinedione, CB1 antagonist, GLP-1 analog, DPP4 inhibitor, statins, fibrates, etc.
Over the years, several drugs have been validated with Physiogenex’s models including PTP1b inhibitor, 11βHSD1 inhibitor, glucokinase activator, adiponectin-like peptide, SCD1 inhibitor, MC4R agonist, CB1 antagonists and intestinal lipase inhibitor.
(1) “Drinking more than one soft drink daily was associated with a 44% greater risk of developing the metabolic syndrome and four out of five components (waist circumference, fasting glucose, hypertriglyceridemia and low HDL-c) of the metabolic syndrome”. Source: Dhingra R, Sullivan L, Jacques PF, et al. Soft drink consumption and risk of developing cardiometabolic risk factors and the metabolic syndrome in middle-aged adults in the community. Circulation 2007; DOI: 10.1161/circulationaha.107.689935. Available at: http://circ.ahajournals.org
(2) McGavock JM, Lingvay I, Zib I, et al. Cardiac steatosis in diabetes mellitus: A 1H-magnetic resonance spectroscopy study. Circulation 2007; 116:1170-1175
(3) Ruberg F. Myocardial lipid accumulation in the diabetic heart. Circulation 2007; 116:1110-1113.
Customized and predictive solutions
- 1st step: define the best conditions
You specify your needs and endpoints. We propose appropriate housing, breeding conditions and/or the best animal strain in order to obtain the right phenotype.
- 2nd step: select the best population
You define, along with Physiogenex experts, the inclusion criteria for the specific target population.
- 3rd step : obtain an animal model to weigh up your competitive advantage
Physiogenex experts select homogeneous groups, providing the best sensitivity and reproducibility, thus detecting even a slight effect of your drug .