New drugs for neurological disease have been noticeably scarce over the last 20 years. Current market offerings are either relatively ineffective or result in unacceptable side effects, resulting in a dramatic unmet need for new treatment options. Moreover, current products only treat symptoms and do not address disease progression. Much of the industry’s inability to produce new drug candidates has been primarily due to the lack of relevant animal disease models. CNS|CRO provides animal models that are progressive and slow developing which translates into more accurate replication of human disease progression. The ability to evaluate candidates at more stages of the disease’s development make our models ideal for identification of early stage treatments. CNS|CRO’s proprietary models demonstrate behavioural characteristics and pathologies associated with human disease progression.

In addition to proprietary offerings, CNS|CRO also offers traditional animal models, as well as histology services and specialty platforms.

CNS|CRO 2017 Models Overview Sheet

CNS|CRO 2017 Models Overview – Information Sheet

CNS|CRO Histology Offerings List

CNS|CRO 2017 Histology Offerings – Information Sheet

CNS|CRO Specialty Platforms

CNS|CRO 2017 Specialty Platforms – Information Sheet

Models Publication List

Models Publication List

CNS|CRO’s proprietary animal model of ALS-PDC (amyotrophic lateral sclerosis-Parkinsonism dementia complex) utilizes a neurotoxin that causes a slowly developing and progressive series of well-defined sequential deficits in mice and rats. The neurotoxin, first documented in humans following dietary exposure to the cycad seed in the 1940’s on the island of Guam, was identified and patented by Neurodyn Inc., CNS|CRO’s parent company. Neurodyn Inc. continues to chemically synthesize the neurotoxin for test use by CNS|CRO.

CNS|CRO Model Advantages & Differentiation

  • The model can be produced in healthy, wild type, out-bred adult animals;
  • Disease process is recreated from its inception, without the induction of genetic lesions that are only representative of a small percentage of the entire patient population;
  • Due to the slowly progressive and sequential development or neurodegenerative deficits in this model, therapeutic screening may be performed over an extended time frame, thus improving outcomes of preclinical studies (e.g. target identification, mechanism of action validations, etc.);
  • Unlike other “environmental” models, CNS|CRO’s model satisfies the basic criterion of etiological validity, with the same factor linked to human disease used for recreation of the disease in animals;
  • Distinct from genetic or transgenic models, CNS|CRO’s animal model mirrors all the essential features of the human condition, from the appearance of behavioural deficits through to biochemical abnormalities.

Validation

Three studies have been conducted which provide conclusive evidence that point-in-time results from CSN|CRO’s slowly progressive PDC model are fully comparable to those generated using conventional models of MPTP and MPP.

Printable Model Information Sheet

ALS-PDC Model – Information Sheet

CNS|CRO’s proprietary animal model of Parkinson’s Disease utilizes a neurotoxin that causes a slowly developing and progressive series of parkinsonism features in rats. First documented in humans following dietary exposure to the cycad seed in the 1940’s on the island of Guam, the neurotoxin was identified and patented by Neurodyn Life Sciences Inc, CNS|CRO’s parent company.

Printable Model Information Sheet

Parkinson’s Disease Model – Information Sheet

CNS|CRO’s unique, development rat model of epilepsy provides a highly reproducible sequence of behavioural and histopathological changes over time. Treated rats have altered EEG, reductions in both generalized and focal seizure threshold, and changes in sleep patterns that are highly reminiscent of those observed in partial complex epilepsy in humans. CNS|CRO’s established rat model of progressive epilepsy development is clinically relevant for the purposes of new drug evaluation including having the ability to dissociate response between male and female animals.

EEG

EEG

CNS|CRO Model Advantages & Differentiation

  • The model is neurodevelopmental in origin, slowly developing and progressive with a latent period prior to onset of clinical signs;
  • Behavioural changes are clinically relevant for partial complex epilepsy (eg. orofacial automatisms; forelimb tremor);
  • Highly reproducible sequence of behavioural and histopathological changes over time which is not possible with the convulsive models (e.g. changes in neurotrophin signalling precede abnormal circuit formation precede hippocampal cell loss);
  • Allows for behavioural, histopathological and neurochemical assessment;
  • This is NOT a model of convulsions. Virtually all other models induce convulsive seizures and, as such, measure an “end state” condition, thus they do not mimic the developmental features of temporal lobe epilepsy (TLE).

Validation

Since this model is not one of convulsive seizures, full validation using existing anticonvulsant drugs is problematic. However studies have been conducted with Topamax (topiramate) and Valproate in this model.

Printable Model Information Sheet

Developmental Epilepsy Model – Information Sheet

Endothelin-1 microinjections (ET-1): Stereotaxic microinjections of picomole quantities of ET-1 can produce defined cortical lesions that correlate with functional loss in specialized brain regions (e.g. unilateral forelimb motor representation area). Injection of ET-1 in the vicinity of the MCA will result in lesions comparable to those observed using the MCAo technique.

CNS|CRO Model Advantages & Differentiation

  • Intensive post-MCAo care results in a >90% survival rate (vs 40-50% in conventional models), allowing long-term neurobehavioural evaluation of a more clinically relevant post-stroke population;
  • Major improvements to the ET-1 technique provides a highly reproducible, predictable, and localizedinjury. Observations can be made up to 2 months post-stroke, thus increasing understanding of therapeutic intervention, and improving chances of detecting the benefits of restorative or rehabilitative therapies;
  • Models are relevant to common problems for post-stroke survivors, with the ability to evaluate in emotionality, cognition, sensorimotor deficits, and learning and memory function.

Validation

NoNO Inc used the CNS|CRO modified MCAo procedure as part of the successful FDA and Health Canada IND approval for their candidate NA-1. The candidate has since successfully concluded Phase IIb clinical trials.

Printable Model Information Sheet

Stroke Model Information Sheet

Neonatal hypoxia-ischemia: Hypoxic-ischemic encephalopathy (HIE) in neonates is a known cause of long-term neurological disability in children. The most commonly utilized animal model of this condition is produced at CNS CRO in 7 day old rat pups by inducing unilateral hypoxia-ischemia (HI; modified Levine model).

Carotid vessel occlusion: CNS|CRO can produce adult models of global ischemia with variable severity in both mice and rats. Occlusion can be either temporary via the use of artery clips, or permanent by suturing the vessel closed. Stroke severity can be further manipulated through the number of arteries targeted.

CNS|CRO Model Advantages & Differentiation

  • Complex behavioural testing paradigms specifically designed for neonatal animals can be interfaced with adult testing and combined with appropriate histology and/or neurochemistry;
  • Rigorous post-operative care protocols maximize survival rates and increase the range and duration of the deficits;
  • Use of a multi-chamber closed system induction apparatus for the HI model provides consistent control, allowing multiple animals from all treatment conditions (if appropriate) to be induced simultaneously, and with minimal separation time from the dam;
  • In adult rodents, temporary or permanent artery occlusion may be performed in 1 to 4 vessels: Lateralized ischemia (occlusion of one carotid artery) Bilateral global ischemia (2-VO; occlusion of both carotid arteries) Complete occlusion (4-VO; occlusion of both carotid and vertebral arteries)

    Printable Model Information Sheet

    Stroke Model Information Sheet

PrePulse Inhibition Chamber

PrePulse Inhibition Chamber

The CNS|CRO rat model of schizophrenia is produced using non-invasive chemical manipulation during perinatal brain development, resulting in a more accurate replication of the human condition. Schizophrenia-specific behavioural alterations include delayed-onset deficits in attentional processing, sensory gating, cognition and social interactions, while pathological investigations have shown changes in cortical dopaminergic markers. Consistent with human epidemiological data, these behaviours and pathological alterations demonstrate gender-specific variation, a phenomenon that is likely due to maturational differences during male and female brain development.

CNS|CRO Model Advantages & Differentiation

  • The model is neurodevelopmental in origin, slowly developing, and progressive;
  • Able to model the three categories of symptoms in schizophrenia:Positive (psychomotor agitation)Negative (social avoidance) Cognitive (maze paradigms/prepulse inhibition) Histopathology is consistent with that observed in clinical populations;
  • Allows for testing of gender-specific therapies due to demonstrated differences between male and female animals.

Printable Model Information Sheet

Schizophrenia Model – Information Sheet

CNS|CRO`s mouse model of neuropathic pain provides a sensitive method for testing therapeutants aimed at modulating pain pathways. Using a spared nerve injury (SNI) paradigm, this model allows for repeated testing as well as assessment of efficacy at various time points post-treatment. Test article administration may be performed via intraplantar injection, topical, gavage, or intra-nasal application.

Printable Model Information Sheet

Neuropathic Pain Model – Information Sheet

Electrophysiology is used to amplify and measure bio-electrical signals caused by movement of ions through cellular ion channels. Because many pathophysiological conditions in the CNS and elsewhere (PNS, heart, cultured neurons) arise from alterations to ion channel activity, electrophysiology provides an invaluable tool to better understand these conditions and to develop drugs to treat them.

CNS|CRO offers a wide variety of electrophysiological services which can be tailored to meet the specific needs of R&D programs. CNS|CRO is also distinct in that it offers both in vitro and in vivo electrophysiological services.

Printable Model Information Sheet

Electrophysiology Offerings – Information Sheet