CN
CN

CN
Central Nervous System & Pain

Overview

 

The CNS & Pain Discovery team provides customer oriented integrated services within our AAALAC accredited animal facility and world class laboratories including a GLP standard laboratory. We strive for highest data quality, consistency, and maximal efficiency.

 

 

Best-in-Class Capabilities

 

  • Functional leaders with disease and/or project leading experience
  • Technical leaders with extensive bench experience
  • Dedicated staff with a good training system
  • International standard instrumentation and SOPs
  • Multiple backups and new capacity expansion on-going
  • Functionally diversified with validation of GPCR, Kinase and ion channel targets

 

 

In Vitro and Ex Vivo Assays

 

  • Ex vivo assays for receptor occupancy, brain slice with functional readout and neuronal recordings (isolated brain cell recordings)
  • Assay development, screening and SAR support for GPCRs, transporters and ion channels
  • Cell line development
  • Electrophysiology assays using automated patch clamp, and manual patch clamp

 

 

Electrophysiology

 

Current capacity

  • IonWorks Quattro: Using 384-well PatchPlates. Daily capacity of around about 3000 data points 
  • QPatch systems: Two QPatch machines, generating up to 60 concentration-response curves per day.
  • Manual patch-clamp for recording from cultured cells: Four rigs in place, current capacity is about 10 concentration-responses curves per day
  • Brain slice recording: One rig is available, capacity is 2-6 cells per day

 

Ion channel targets expansion

  • Stable cell lines:
    • HERG-HEK
    • 1-CHO
    • P2RX7-CHO
    • TRPV1-HEK
    • Nav1.4-CHO
    • Nav1.6-CHO
    • Nav1.7-CHO

 

  • Final constructs: 
    • Nav1.8
    • nAChR
    • 7-Ric3
    • Stim1/Orai1
    • Stim1/Orai3
    • Kir3.1-3.4
    • TRPV4

 

 

In Vivo Pharmacology Models & Translational Science

 

Due to the importance of translational science in CNS/pain drug discovery, we aim to set up the capability to help the success of clinical phase II. So far, we have developed a rat MIA model measured with weight-bearing which is considered to be the most relevant animal model for osteoarthritis. A receptor occupancy method was also developed to provide target engagement evidence.

 

Besides translational science, we have a built broad spectrum of animal models for CNS diseases and chronic pain to support a systematic approach in vivo drug discovery and development with multiple endpoints including: behavior, efficacy, PK/PD, safety, biomarker assays, and pathology.

 

  • Schizophrenia: Prepulse inhibition of startle (PPI), conditioned avoidance response (CAR), Morris water maze,delayed alternation task (Y-maze),novel object recognition (NOR), attentional set shifting
  • Neurodegenerative diseases (e.g. AD & PD):Scopolamine induced cognitive deficits, 6-OHDA unilateral lesion model; L-DOPA induced dyskinesia in 6-OHDA PD rats, HIC (haloperidol induced catalepsy)
  • Anxiety & depression: Vogel conflict test, open field (sLMA, cognition and anxiety), elevated plus maze, forced swimming test, learned helplessness
  • PK/PD for target engagement and MOA, biomarkers, chemical, CSF, in vivo e-phys, EEG (in development), safety pharmacology, Irwin test for general neurological liabilities

 

 

Translational Models of CNS/Pain

 

  • Monosodium iodoacetate (MIA)
  • In vivo brain receptor occupancy measurement

 

 

Pain Models & Measurements

 

Acute nociception

  • Tail flick
  • Hot plate

 

Acute inflammatory pain

  • Formalin
  • Capsaicin induced tactile allodynia
  • Carrageenan

 

Chronic inflammatory pain

  • CFA

 

Chronic neuropathic pain

  • SNL: spinal nerve ligation (Chung)
  • CCI: chronic constriction injury
  • PNL: partial nerve ligation
  • Diabetic/chemotherapy pain

 

Post surgical pain

  • Brennan model in rats

 

Visceral pain

  • Acetic acid writhing in mice

 

Itching model

  • Compound 48/80 induced Itching model in mice

 

 

CNS Models & Measurements

 

Safety assays

  • Irwin test
  • FOB (functional observational battery)
  • Spontaneous locomotor activity
  • Rotarod test
  • Grip strength

 

Cognitive function assays

  • Morris water maze
  • Passive avoidance
  • Delayed alternation task (Y-maze)
  • Novel object recognition (NOR)
  • Attentional set shifting

 

Schizophrenia

  • Prepulse inhibition of startle (PPI)
  • Conditioned avoidance response (CAR)
  • PCP or Amephtamine induced hyperlocomotor activity
  • SubPCP or NeoPCP induced cognitive deficits

 

Anxiety and depression

  • Vogel conflict test
  • Open field
  • Elevated plus maze
  • Forced swimming test
  • Learned helplessness

 

Parkinson’s Disease (PD)

  • HIC (haloperidol induced catalepsy
  • 6-OHDA unilateral lesion model
  • Akinesia model in 6-OHDA PD rats
  • L-DOPA induced dyskinesia in 6-OHDA PD rats

 

Alzheimer’s Disease (AD)

  • Scopolamine induced amnesia models

 

 

Learn More about In Vivo Pharmacology & PK/PD

 

 

 

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