Biological Materials Used to Induce Disease and Create Validated CNS Study Models

Feb 18 2013

In addition to small molecules, various biological materials and biosimilars are being employed both in in vivo CNS efficacy studies and in order to create models of neurological and psychiatric diseases at Charles River. These therapeutic interventions include administration of proteins (antibodies, peptides, growth factors), RNA (RNA interference with siRNA) and stem cells (human embryonic, mesenchymal, neuronal).

Administration routes that have been validated include not only the traditional routes (i.v., s.c., i.p., p.o.), but also intraparenchymal (directly to the brain tissue), intrathecal (delivery to subarachnoid space at a desired location in spinal column), intracerebroventricular (delivery into ventricular space) and intracisternal (direct injection through cisterna magna) routes. In addition to the various validated administration routes, we have also validated the ability to use viral vectors to deliver proteins that are detrimental to neurons in specific brain regions (i.e., dopaminergic neurons in the substantia nigra in Parkinson’s disease).

Administration duration can vary between acute injections (from seconds to hours) to chronic infusion with minipumps (from weeks to months). Biological samples are prepared and handled in a dedicated cellular laboratory by personnel experienced in the processing of biologics for in vivo studies and sterile minipump loading, as well as sterile processing of dosing solutions of antibodies and growth factors. We can also provide extraction and preparation of bone marrow and splenic cells from tissue samples.

Surgical manipulations for administration of biological therapies include state-of-the-art surgical stations with physiological monitoring capabilities (laser Doppler, blood gases, BP) and Biosafety Level 2 facilities for working with cells, viruses and proteins.

For biodistribution, efficacy and safety studies, our dedicated radiochemistry, SPECT/CT and PET/CT laboratory and state-of-the-art Category B radiochemistry laboratory are equipped with gamma and scintillation counters, SPECT/CT scanner and PET/CT scanner.

Full histology and biomarkers are also optional endpoints that are available in the study of diseases of the CNS and PNS.

To learn more about our models of neurological and psychiatric disease, please contact us at askcharlesriver@crl.com.

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