BONE & MUSCULOSKELETAL DISORDERS

Rheumatological diseases and musculoskeletal disorders are major causes of non-fatal injuries in human. This therapeutic area covers bone fractures, cartilage defect, muscle injuries, rheumatic disorders such as osteoarthritis, or even autoimmune disorders like rheumatoid arthritis.

Non-human primates naturally develop the same pathologies as in humans, because of similarities in their morphology and in the biomechanical properties of bones, joints and tissues. Furthermore, the similarity of their immune system makes the NHP an excellent model to test the efficacy of immunotherapies targeting rheumatological conditions.

By taking advantage of these features, Cynbiose has built an expertise in this particular therapeutic area in early exploratory studies as well as predictive efficacy models.

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Efficacy studies
  • Post-traumatic osteoarthritis model
  • Cartilage defect
  • On-demand preclinical models: contact us to discuss your needs
Exploratory studies
  • Pharmacokinetics
  • Pharmacodynamics
  • Early toxicology studies

Post-traumatic osteoarthritis model

 

This model induces ostearthritis (cartilage damage) and tissue responses that closely replicate the pathology as in humans.

It effectively mimics the early stages of human post-traumatic osteoarthritis (reduction of the cartilage thickness by 30%).

 

Model

  • Species: Cynomolgus macaque (Macaca fascicularis)
  • Model based on a surgically-induced instability of the knee joint

Type of test item

  • Anti-inflammatory NCE
  • Anti-inflammatory biologics
  • Cartilage repair, chondrostimulant

Efficacy readouts

  • Daily clinical assessment : pain, locomotion, joint aperture angle
  • Clinical pathology
  • Sampling : blood, synovial lavage, …
  • Monitoring and automated quantification of the injuries by imaging modalities: µCT arthrography, MRI. Possibility to use advanced MRI sequences to investigate the cartilage structure.
  • Histopathology
  • Synovial, seral and urine specific biomarkers
  • On-demand and customized readouts

Validation of the model

  • Cartilage thinning observed by µCT arthrography
  • Monthly injection of Ostenyl Plus decreases the symptoms

Scientific publications

  • Eurostars innovative program, Cynbiose (Coordinator)

Scientific partners

  • Specializing preclinical CRO in tissue analysis (skin, bone and cartilage)
  • VOXCAN
  • CERMEP
  • CREATIS, CNRS UMR-5220, INSERM U1206, Université Lyon 1

Cartilage defect

A model of focal cartilage defect to assess the efficacy of biomaterials (hydrogels) or cell-based reconstructive therapies.

 

Model

  • Species: Cynomolgus macaque (Macaca fascicularis)
  • Surgically induced model: focal defect of the knee’s cartilage

 

Type of test item

  • Biomaterials (e.g. hydrogel)
  • Cell type such as articular chondrocytes, adipose-derived stem cells, human Mesenchymal Stem Cells (MSCs), …
  • Cell printing technologies

Efficacy readouts

  • Non-invasive imaging follow-up: µCT arthrography, MRI
  • Daily clinical assessment: pain, locomotion
  • Clinicalpathology
  • Sampling : blood, synovial fluids, …
  • Histopathology, IHC
  • Biomarkers
  • On-demand and customized readouts

Validation of the model

  • Consistent results between histology and µCT arthrography
  • Cell-loaded (autograft) and cell-free hydrogel

Scientific publications

  • Dufour A., Verset M., Cohendet A., Buffier M., Rioult M., Contamin H., Groult E., Mallein-Gérin F. Use of autologous chondrocyte-seeded hydrogel to treat focal cartilage defect in non-human primate.
    International Cartilage Repair Society 2018 14th World Congress, 9-12 April 2018, Macao (China).  Poster
  • Dufour A., Verset M., Cohendet A., Buffier M., Rioult M., Contamin H., Perrier-Groult E., Mallein-Gerin F. Repair of Osteochondral Defect in a Non-Human Primate Model Using Autologous Chondrocyte-seeded Hydrogels.
    European Cells & Materials 13rd Conference, 25-28 June 2018, Davos.

Scientific partners

  • Specializing preclinical CRO in tissue analysis (skin, bone and cartilage)
  • VOXCAN
  • CERMEP
  • IBCP (UMS3760)

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