Covid-19 CRO Service: Physiogenex Coronavirus Disease – NASH Hamster model

◆Summary

France CRO Physiogenex, partner of CLEA Japan, Inc. has developed Coronavirus Disease 2019 CRO service using a diet-induced obese NASH hamster model.

This obese NASH Hamster model shows greater severity of COVID-19 as observed in obese humans. Given its high similarity with the human context, this model is useful for preclinical study evaluating efficacy of drugs targeting COVID-19.

※NASH: Non-alcoholic Steatohepatitis
※This hamster is prepared only for this contract research service. We do not sell it as our animal models.

Table of contents: ◆COVID-19 in obese NASH Hamster ◆Example: Study design (w/ Free Choice Diet) ◆The mechanism of COVID-19 infection and lung damage ◆Characteristics of the Physiogenex obese NASH Hamster model　 ◆What is Physiogenex ◆FAQ ◆Inquiry

◆COVID-19 in obese NASH Hamster

Physiogenex obese NASH Hamster model infected with SARS-CoV-2 shows greater lung damages.

・HE stain of Lung
　　　　　No infected　　　　  Infected with normal diet 　    Infected with Free Choice diet


・Sirius Red stain of Lung

  Infected with normal diet       Infected with Free Choice diet        lung fibrosis quantification   


Reference：
・The incidence of COVID-19 in patients with metabolic syndrome and non-alcoholic steatohepatitis: A population-based study
　Ghoneim et al. Metabolism 2020

・Pathogenesis and transmission of SARS-CoV-2 in golden Syrian hamsters
　Sia et al. Nature 2020 

・Spike protein recognition of mammalian ACE2 predicts the host range and an optimized ACE2 for SARS-CoV-2
　Luan et al. BBRC 2020

◆Example: Study design (w/ Free Choice Diet)

Obesity and NASH is induced by a Free Choice diet* in hamster before infection with Sars-CoV-2.


* Free Choice Diet
The Free Choice Diet is that the subject animals can choose between normal chow diet/normal water and high fat/cholesterol diet and 10% fructose rich water, in the same housing cage. It favors hyperphagia in hamster (which cannot be induced with a high fat diet alone) and induces obesity, NASH and heart failure with preserved ejection fraction.

◆The mechanism of COVID-19 infection and Lung damage

Normal : ACE2 sustains balance of the vascular structure by connecting Ang II
・Serum Ang I is converted to Ang II by ACE.
・Ang II activates the AT1R, AT2R pathway
　→　Promotes vasoconstriction, inflammation, Fibrosis and ultimately lungs injury
・Ang II is converted to Ang1-7 by ACE2
　→ Ang1-7 activates the Mas pathway
　→ Protective against lungs injury.

Infected : SARS-Cov-2 binds ACE2
・Ang II levels increases and favors the proinflammatory/profibrotic AT1R pathway.
・SARS-Cov-2 impairs Ang II conversion to Ang1-7.
　→ Cannot be protective against lungs injury.

◆Characteristic of the Physiogenex obese NASH Hamster Model

・NASH
 Hepatic fibrosis          Ballooning     Inflammation       Ballooning   Bridging fibrosis



・Decreasing lung Inf-arpha / Increasing Inflammatory IL-6 cytokine


・Decreasing Serum ACE2 activity


Reference：
・Circulating ACE2 activity correlates with cardiovascular disease development
   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5843890/

・Heart Failure with Preserved Ejection Fraction（HFｐEF）


Reference of the NASH Hamster model:
Elafibranor improves diet-induced nonalcoholic steatohepatitis associated with heart failure with preserved ejection fraction in Golden Syrian hamsters
　Briand et al. Metabolism 2021

More details of Physiogenex CRO service NASH Hamster model

◆What is Physiogenex:

Physiogenex provides preclinical in vivo and ex vivo CRO services and consulting in metabolic disorders such as obesity, diabetes, NASH, fibrosis, diabetic nephropathy, cardiovascular complications, dyslipidemia and atherosclerosis.

Not only the CRO service provider, Physiogenex can be a partner to develop the animal models and assess technics as needed. In addition, Physiogenex can dedicate to support your study with their various specialists of R&D, preclinical study, additional study after sales, and reevaluation of pharmacometrics. Moreover, Physiogenex can execute in vivo preclinical imaging service, too.
（From Physiogenex Homepage in 2017）
Physiogenex Service:Details of CLEA Japan support and Service Condition

◆FAQ

How is the study running?

Do we need to have an agreement with 3 organizations, included CLEA Japan also?

How long does it take to do Hamster DIO?

Can Physiogenex use non-NASH hamster for this service?

Can Physiogenex do the wiping qPCR analytics without animal scarification?

Can Physiogenex report be good enough to use for such as IND submission?

Do we need to submit a study protocol in the first place?

What variant of the Covid 19 does Physiogenex use?

When can Physiogenex start the study?

◆Inquiry