With the rise in drugs targeting various neurodegenerative diseases, it becomes crucial to assess the actual bioavailability of these products at the expected region of interest, that is, the Central Nervous System.
Cynbiose developed an expertise in the in vivo and ex vivo assessment of CNS drug bioavailability in a relevant preclinical model the non-human primate.
Objectives
- Assess the relative bioavailability of a product in the CNS (CSF, local extracellular fluid, whole brain) compared to the plasmatic concentration
- Characterize proteins or genes of interest in endothelial or epithelial cells of the NHP blood-brain barrier
- Assess the crossing of the Blood-brain barrier (BBB) for drugs targeting tumors of the Central Nervous System (CNS)
Methods
- Classic or intrathecal ROA
- Repeated sampling of CSF and plasma in non-human primate
- Microdialysis in specific part of the brain in awake NHP
- Characterization of NHP brain microvessels or choroid plexus by proteomic, transcriptomic or in-situ hybridization
- MRI-guided surgeries, CSF quantification
Readouts
- PK measurements in whole organs, plasma, CSF, brain dialysate
- Cytokines measurement in various medium
- Preclinical imaging
Type of drugs
- Small molecules
- Biologics
- Immunotherapies targeting the CNS
- Oligonucleotides, ASO
- Peptides
- Viral-vector based gene therapies
Scientific publications
- Thiollier, T., Wu, C., Porras, G., Bezard, E., Li, Q., Zhang, J., & Contamin, H. (2018). Microdialysis in awake macaque monkeys for central nervous system pharmacokinetics. Animal Models and Experimental Medicine, 1(4), 314–321. DOI
- Thiollier, T., Wu, C., Contamin, H., Li, Q., Zhang, J., & Bezard, E. (2016). Permeability of blood-brain barrier in macaque model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson disease. Synapse, 70(6), 231–239. DOI
Scientific partners
- Motac Neurosciences: Motac provides highly – specialised preclinical research services to pharmaceutical and biotechnology companies that are developing new treatments for neurological diseases, particularly neurodegenerative conditions like Parkinson’s disease or other motor and cognitive disorders.
- Hawkcell : HawkCell offers MRI imaging services that revolutionize animal diagnostics (up to 150 kg) and preclinical research. From optimized imaging protocols to image quantification and MRI sensors, the entire acquisition chain has been redesigned to meet the needs of veterinary medicine and research.
