Neurofit - Preclinical PNS And CNS Drug Discovery

Neurofit is a Contract Research Organisation (CRO) specialising in the evaluation of treatments for peripheral and central nervous system disorders.

Neurofit offers a long list of validated in vivo and in vitro methods and disease models for drug screening and provides customers with high quality research data and reports. Methods and protocols can of course be adapted to client's request.

IN VITRO MODELS AND ASSAYS

Neurofit has developed a large range of in vitro models and assays for assessment of drug-induced neurotoxicity, neuroprotection and neurotrophic activity. These assays are based on primary cultures of neurons: cortical, hippocampal, mesencephalic neurons, sensory neurons or spinal cord motor neurons. Neurofit also offers two co-culture models: Schwann cells with sensory neurons and rat nerve with human muscle as well as glial cell cultures (oligodendrocyte precursor cells and astrocytes).

Neurofit can study the protective, regenerative and disruption effects of test compounds.

• Basal neuronal survival and neurite outgrowth using cortical, hippocampal and spinal motor neurons
• Stroke and Amyotrophic Lateral Sclerosis (ALS): excitotoxic effect of NMDA or glutamate on cortical and spinal motor neurons
• Chemotherapy induced-neuropathy models using anti-mitotic drug as toxic agent: purified sensory neurons or sensory neurons and Schwann cells co-culture intoxicated with cisplatin, vincristine or taxol and spinal motor neurons intoxicated with vincristine
• Parkinson's disease on mesencephalic neurons intoxicated with MPP+
• Multiple sclerosis: proliferation of oligodendrocyte precursor under different conditions
• Nerve functionality: human muscle - rat nerve co-culture

IN VIVO MODELS AND ASSAYS FOR DRUG SCREENING IN NEUROLOGY

Neurofit has developed powerful testing methods in rodents to assess the neurotoxic, neuroprotective or neurotrophic effects of drug candidates. Studies may include quantitative behavioural measurements or analysis of effect upon neurodegenerating nerve fibres or nerve cells.

• Multiple sclerosis: Experimental Autoimmune Encephalomyelitis (EAE) and Delayed-Type Hypersensitivity (DTH) in rat
• Rheumatoid arthritis: collagen induced arthritis in rat
• Epilepsy: PTZ-model in mice
• Pain and neuropathic pain: diabetes-induced neuropathic pain, diabetic painful neuropathy
• Peripheral neuropathies: sciatic nerve crush (traumatic neuropathy), streptozotozin (STZ) rats (diabetic neuropathy), antimitotic-induced neuropathies (chemotherapy-induced neuropathy)

Neurofit can combine these disease models with several different tests to evaluate motor deficits including motor coordination tests such as Rotarod, beam walk test, gait analysis, grid test, hanging test and string test; sedation tests detecting spontaneous locomotor activity in the open-field test; sensitivity tests for allodynia - cold bath tests, hot plate tests at 38°C and Von Frey tests; sensitivity tests for hyperalgesia - hot plate tests at 52°C and Randall-Sellito tests; and EMG evaluations such as sensory and motor nerve conduction, Compound Muscle Action Potential (CMAP) and h-wave reflex.

IN VIVO MODELS AND ASSAYS FOR DRUG SCREENING IN PSYCHIATRY

Neurofit offers a variety of well-accepted behavioural tests to assess the potential anxiolytic, antidepressant or antipsychotic effects upon cognition i.e. memory or learning of test compounds.

• Anxiety tests: Light-dark boxes and the marble burying test in mice and the Elevated plus maze test in mice and rats
• Depression: The forced swimming test in mice and rats
• Schizophrenia: MK-801 induced hyperactivity in mice
• Cognition: Object recognition tests in mice and rats and T-maze in mice

IN VIVO MODELS AND ASSAYS FOR GENERAL SIDE EFFECT TESTS

Neurofit proposes several models to evaluate side effect of novel compounds:

• Sedation: spontaneous locomotor activity in the open-field
• Cognition dysfunction: object recognition tests in mice and rats and T-maze in mice
• Motor coordination: rotarod
• Addiction: conditioned place preference test in mice
• Maximal Tolerated Dose (MTD, non-GPL)

HISTOLOGICAL ANALYSIS

Neurofit offers a computer assisted histological platform to investigate neurodegeneration on peripheral nerves with morphometric parameters: axonal area, relative myelin thickness, fiber size distribution, fibers density and percentage of degenerated fibers.

Neurofit implements standard colorations as well as specific immunostaining, on paraffin and cryo-section.