CARDIOVASCULAR & METABOLIC DISORDERS

Cardiometabolic diseases are the 1st cause of death worldwide, representing around 30% of all deaths worldwide according to the WHO. The CMDs include different pathologies such as cardiovascular diseases (coronary heart diseases, hypertension, heart failure and strokes, …) and metabolic disorders (diabetes, NAFLD, NASH, dyslipidemia, obesity).

Major advantages of the Non-Human Primates for understanding CMDs are their genetic, metabolic, and physiologic similarities with humans. Indeed, NHP develop metabolic diseases in the wild and are sensitive to the same risk factors than humans. The ability to manage diets (Western diets for example), control the environment, select phenotypes of interest represents a major asset for preclinical research. Moreover, the gut microbiome is a known risk factor for CMD, and the induction of dysbiosis can be used to refine the predictive powers of our translational POC models.

 

Share this!
Efficacy studies
  • Diet-induced atherosclerosis
  • Post-ischemic heart failure
  • On-demand preclinical models: contact us to discuss your needs
Exploratory studies
  • Pharmacokinetics
  • Pharmacodynamics
  • Early toxicology studies

Diet-induced atherosclerosis

This diet-induced model mimics human atherosclerotic clinical conditions such as atherosclerotic lesions, increased risk of cardiovascular events and plaque formation.

Correlations between metabolic activity, inflammation, lymphocyte infiltration and vulnerable plaque markers were observed in the carotids and aortic arch, similar to the clinical setting.

This translational model is thus designed to test the efficacy of anti-atherosclerotic drugs and of biomarkers for risk stratification of the patients.

 

Model

  • Species: Cynomolgus macaque (Macaca fascicularis)
  • Diet-induced model (High fat, High Cholesterol)

Type of test item

  • Cardioprotective therapeutic strategies
  • Immunotherapies
  • Cell therapies
  • Oligonucleotide, ASO
  • Gene therapies, Viral vector-based therapies
  • Recombinant protein
  • Anti-inflammatory drugs

Efficacy read-outs

  • Clinical follow-up: clinical observation, body weight, food consumption
  • Noninvasive hemodynamic recordings
  • Clinicalpathology
  • Detailed lipidemia and cholesterolemia profile
  • Immunomonitoring
  • Biomarkers
  • Noninvasive imaging follow-up (ultrasound scan, MRI, PET scan) for precise detection and localisation of atheroma plaques
  • Histopathology, IHC
  • PET scan for atherosclerosis-related neuroinflammation

 

  • On-demand and customized readouts

Scientific publications

  • Debatisse J., Makris N., Di Cataldo V., Portier K, Verset M., Wateau O., Langlois J.B., Lamberton F., Ibarolla D., Lavenne F., Le Bars D., Troalen T., Contamin H., Cho T.H., Canet-Soulas E. Supervised clustering analysis for quantification of neuroinflammation using [11C]PK11195 PET in young and old controls, and atherosclerotic non-human primates.
    13th European Molecular Imaging Meeting (EMIM), 20-23 March 2018.
  • Di Cataldo et al. Markers of vulnerable plaques in Non-Human Primates under atherogenic diet. World Molecular Imaging Congress, 7-10 Sept 2016, New York.
  • Di Cataldo et al. MR and PET/CT Imaging using to stratify cardiovascular risks in Non-Human Primates under atherogenic diet. 11th International Conference on Cerebral Vascular Biology, 6-9 July 2015, Paris.

Scientific partners

  • CERMEP – Imagerie du Vivant, Lyon, France
  • CREATIS, CNRS UMR-5220, INSERM U1206, Université Lyon 1, France
  • CarMeN laboratory

Post-ischemic heart failure

This unique minimally invasive acute myocardial ischemia/reperfusion model mimics physiologically acute effects of myocardial infarction (Acute coronary syndrome – ACS). This model displays coronary occlusion and reperfusion as in human patients, confirmed by advanced cardiac imaging and histopathological changes. The longitudinal analysis of chronic effects (left ventricular dysfunction) can be used for the pharmacological investigation of cardioprotective drugs.

 

Model

  • Species: Rhesus monkey (Macaca mulatta), Cynomolgus monkey (Macaca fascicularis)
  • Surgically induced model by endovascular catheterization with a trained interventional cardiologist.

 

Type of test item

  • Cardioprotective therapeutic strategies
  • Post-myocardial-infarction (MI) and anti-heart-failure drugs
  • Cell therapies
  • Immunomodulatory agents
  • Ultrasound contrast agent, radioactive tracers
  • Therapeutic interventions for protective properties

Efficacy read-outs

  • Clinical follow-up: clinical observation, body weight, food consumption
  • Noninvasive hemodynamic recordings
  • Clinical pathology
  • Immunomonitoring
  • Heart failure biomarkers
  • Monitoring of cardiac function: ultrasound imaging, scanner, MRI
  • Histopathology, IHC
  • On-demand and customized readouts

Scientific publications

  • Drut A. Establishment of a minimally-invasive post-ischemic model of chronic heart failure in cynomolgus monkeys (Macaca fascicularis).
    In: 12th European Primate Veterinarian (EPV) annual symposium, 27-28 Sept 2012
  • Contamin H. et al. A minimally-invasive closed chest myocardial occlusion-reperfusion model in rhesus monkeys (Macaca mulatta): monitoring by contrast-enhanced ultrasound imaging. Int J Cardiovasc Imaging. 2012 Mar; 28 (3): 531-542.

Scientific partners

  • CERMEP
  • CREATIS, CNRS UMR-5220, INSERM U1206, Université Lyon 1
  • CarMeN laboratory

On-demand preclinical models: contact us to discuss your needs

The selection of the appropriate animal model to evaluate the efficacy of your drug candidates is critical to your preclinical research success.

Cynbiose is committed to providing you with clinically relevant animal models, outstanding surgical and technical capabilities as well as high-quality data.

For more information, visit our specific page dedicated to customized efficacy models.

We’d be pleased to discuss your needs and projects. Feel free to contact our teams.

Pharmacokinetics

Pharmacokinetics

  • Circulating drug kinetics following most routes of administration (more information)
  • Cutting-edge expertise for in vivo central pharmacokinetics 
    • Blood sampling
    • Cerebrospinal fluid (CSF) drug levels
    • Brain microdialysis to monitor neurotransmitters, drugs or metabolites in the extracellular cerebral fluid.
      Discover our proprietary platform Kine C3

Clinical follow-up and Bioanalysis

  • Daily clinical monitoring for the early detection of adverse effects
  • Monitoring of physiological parameters and other biomarkers of interest
  • Bioanalysis (more information)

Pharmacodynamics

More information here.

Early toxicology studies

Type of studies

  • Single and repeated doses, dose escalating studies
  • Immunosafety, immunogenicity
  • Pulmonary tox and respiratory function
  • Dose Range Finding (DRF)
  • Maximum Tolerated Dose (MTD)

Type of test item

  • Immunotherapies
  • Antibodies, ADC, …
  • Cell therapies, gene therapies, oncolytic virus
  • Oligonucleotides, antisense oligonucleotides
  • Therapeutic vaccines such as DNA vaccines, RNA vaccines
  • Recombinant proteins, recombinant enzymes
  • Peptides
  • Oncolytic viruses (BSL2 biocontainment, GMO C2)
  • Small molecules, ….

non-exhaustive list