CNS CRO FOR TRANSLATIONAL DATA

One stop shop CRO for CNS drug discovery 01

Neuroservices Alliance is a One Stop Shop CNS CRO for translational data, providing pharmaceutical industries with functional readouts in neuro-pharmacology. Data are generated from complementary CNS platforms : in silico dynamic ligand-receptor modeling, in vitro & in vivo CNS electrophysiology and Behavioral tests.

Empowered by a strong college of experts, our integrated functional data from Rodent and Human tissues accelerate CNS and Pain research programs thanks to fast and robust lead selection & optimization, investigation of MOA, and validation of target engagement.

Complementary CNS platforms for translational data
Functional readouts for
functional data
A team of strongly experienced neuroscientists

Value offer for
CNS drug discovery 02

We Deliver more than data
Mechanism
of action
Efficacy
Target
Engagment
  • Clear understanding of Targets and MOAs
  • Pharmacological efficacy
    with functional data
  • Drug Repositioning
  • In vitro/In vivo Efficacy in Tg animals/disease models
  • Cross-species translation
    with Human ex-vivo data
  • Functional CNS Safety
    assessment
Commitments
  • Quality Robust & reproducible data
  • Short Turnaround Large bandwidth & top level platforms
  • Interaction Interactive & expert support all along the study
  • Expertise > 40 cumulated years of experience in neuropharmacology
Benefits
  • One-Stop shop CRO
    for CNS
  • Complementary platforms
    & expertises
  • Combined readouts for
    decision making
  • Risk mitigation for
    clinical trials

Therapeutic
Areas 03

Unique Expertise in neuropharmacology
In Vitro
Oscillation Activity Profiling

Hippocampal slice from WT rats/mice and Tg mice

  • Chemically-induced oscillations:Kainate-induced or carbachol-induced oscillations
BIOMARKER: Gamma oscillations
MOA Investigation

Hippocampal slice from WT rats/mice and Tg mice

  • Spontaneous/evoked firing in specific brain structures*
* Lateral Habenula (LHb)/Striatum/ Dentate Gyrus (DG) / Amygdala / Dorsal Raphe
In Vivo
Behavioral Profiling & Screening

Schizophrenia Apomorphine test/ Amphetamine hyperactivity/ MK-801 hyperactivity/ Phencyclidine (PCP) hyperactivity/ MK801 amnesia in Y-maze/ MK-801 social deficit

Pharmacodependence / Addiction Behavioral sensitization/ Conditioned place preference (CPP)/ Opiate withdrawal/ Benzodiazepine withdrawal/ Alcohol intake

Attention Deficit/Hyperactivity Disorder (ADHD) Impulsivity. Delayed Discounting Task (DDT)/ Two-choice visual discrimination task (2-CVDT)

Anxiety – Stress Elevated plus maze (EPM)/Four-plate/Stress-induced anxiety in EPM/ Stressinduced hyperthermia (SIH)

Anxiety – Obsessive Compulsive Disorder (OCD) Marble burying test

Bipolar disorder Amphetamine/Chlordiazepoxide hyperactivity

Depression Forced swimming test (FST)/ Tail suspension test (TST)

Fear & Anxiety MOA

In vivo freely-moving or Head-fixed rodents

  • Local Field Potential recordings
  • Deep electrode recordings

in Lateral Habenula (LHb) /Striatum/ Dentate Gyrus (DG)/Amygdala /Dorsal Raphe In vivo freely-moving or Head-fixed rodents

  • Simultaneous multisite recordings combined with behavior test & Optogenetic
In Vitro
INVESTIGATION OF PRO- OR ANTI-EPILPTIC EFFECT ON EPILEPTIFORM DISCHARGES

Hippocampal slice from WT rats/mice and Tg mice

  • Chemically-induced Epileptiform Discharges (ED): Zero-magnesium-induced ED, 4-AP induced ED, bicuculline-induced ED, NMDA induced ED
MOA Investigation

Hippocampal slice from WT rats/mice and Tg mice

  • Determination of site of actions
  • Evoked excitatory post-synaptic current (EPSC)
  • Spontaneous activity and miniature currents Paired-pulse protocols
  • Paired-pulse protocols
  • Customized protocols (specific antagonists or exogenous application of a receptor ligand
In Vivo
Screening Anticonvulsant Drugs

Mice

Pentylenetetrazole (PTZ)-induced seizure model

  • Parameters: Doses of PTZ inducing a clonic seizure and a tonic-clonic seizure.
In Vitro
COGNITIVE PROPERTIES PROFILING

Hippocampal slice from WT rats/mice and Tg mice

  • Long-Term Potentiation
  • Long-Term Depression
  • Paired-Pulse Facilitation
  • Basal synaptic transmission
NEURONAL PLASTICITY INVESTIGATION

Hippocampal slice from WT rats/mice and Tg mice

  • LTD/LTP “crossover point”
OSCILLATORY ACTIVITY PROFILING

Hippocampal slice from WT rats/mice and Tg mice

  • Pharmaco-induced oscillations: Kainate-induced or carbachol-induced oscillation
BIOMARKER: Gamma oscillations
In Vivo
Behavioral Profiling & Screening

Learning & Memories

  • Spontaneous alternation in Y-maze
  • Novel Object Recognition (NOR) test
  • Social recognition
  • Passive avoidance
  • Habituation in open-field
  • Morris Water Maze

Alzheimer Disease ; Models: Memory deficit induced by scopolamine / Memory deficit in APP-Tg2576 mice
Attention : Two-choice visual discrimination task
Impulsivity : Delayed Discounting Task (DDT)
Vision : Optomotor test

MOA INVESTIGATION

In vivo freely-moving or Head-fixed rodents

  • Local Field Potential recordings
  • Deep electrode recordings

in Cortex, Striatum, Hippocampus, Cerebellum

  • Simultaneous multisite recordings combined with behavior test & Optogenetic
In Vitro
FIRING ACTIVITIES PROFILING

Slices from WT rats/mice & Tg mice

  • Spontaneous firing recording in Cerebellum, Substantia Nigra/
    Motor cortex/ Spinal cord (ventral horn)
HUNTINGTON DISEASE PROPERTIES PROFILING

Slice from WT rats/mice and Tg mice (R6/2, zQ175)

  • Active/Passive membrane properties
  • Spontaneous or miniature excitatory
    postsynaptic currents (spEPSC or mEPSC )
  • Evoked (Electrical stimulation)

in Cortico Striatum

  • LTP in Hippocampal slice
OXYGEN GLUCOSE DEPRIVATION (OGD) MODEL

Hippocampal slice from WT rat

  • Evoked-responses (fEPSP and PS)
In Vivo
Behavioral Profiling & Screening
  • Spontaneous activity in open-field
  • Rotarod
  • Grip strength
  • Bar test
  • Inclined plane test
  • Negative geotaxis
  • Contact righting reflex
  • Parkinson Disease Models: MPTP: Motor deficit DA depletion, 6-OHDA unilateral lesion
  • Huntington disease Model: Motor deficits induced by 3-NP, R6/1 mice
  • Amyotrophic Lateral Sclerosis (ALS) model: SOD mice/rats
  • Charcot-Marie-Tooth Disease (CMT) model : PMP22 rats
  • Neuroinflammation: lipopolysaccharide (LPS)-treated mice
  • Alzheimer Disease Models: Memory deficit induced by scopolamine / Memory deficit in APPTg2576 mice
In Vitro
ION CHANNEL PROFILING

DRG from naive and Neuropathic animals (CCI)

  • Action potential and current recording

Channels: Na+/Ca2+/K+

SPINAL CORD FIRING ACTIVITY PROFILING

Spinal cord slices from naive and Neuropathic animals (CCI)

  • Spontaneous firing
  • Pharmaco-induced model:
  • Capsaicin-evoked neuronal firing
BRAIN FIRING ACTIVITIES PROFILING
  • Spontaneous firing recordings

in VTA and PAG (periaqueductal gray matter)

MOA INVESTIGATION

Spinal cord slices from naive and Neuropathic animals (CCI)

  • Spontaneous firing Miniature inhibitory postsynaptic currents (mIPSCs)
  • Miniature excitatory postsynaptic currents (mEPSCs)
  • Evoked protocol with/without dorsal rootlets
HUMAN ANALGESIC EFFECT PREDICTION

Human DRG from Normal and Chronic Pain Donors

  • Rheobase
  • Action potentials
  • IC50 determination

Channels: Nav (total), Nav 1.7, Nav 1.8, TRPV1, TRPA1, Kv, Cav

HUMAN DRUG SELECTIVIY TARGET IDNTIFICATION

Human DRG from Normal and Chronic Pain Donors

  • Calcium imaging with Electrical Field Stimulation:
  • Cells expressing TTX-S vs. TTX-R
  • A delta-like vs. C-like neurons
  • Cold- vs. heat-sensing neurons
  • Calcium imaging without Electrical Field Stimulation:

Channels: TRPV1, TRPA1, TRPM8, ASIC, TRPV1, P2X, Opioid receptors

HUMAN PERIPHERAL NEUROPATHY NEUROTOXICITY

Human DRG

    Calcium Imaging:

  • Sensitization of Electrical Field Stimulation-induced responses
  • Sensitization of TRPV1 / TRPA1
In Vivo
NEUROPATHIC MODELS:

Chronic Constriction Injury (Bennett model)

Spinal Nerve Ligation (Chung model)

BRAIN FIRING ACTIVITIES PROFILING

In vivo freely-moving rodents

  • Local Field Potential recordings
  • Deep electrode recordings
  • Spontaneous firing recordings

in VTA and PAG (periaqueductal gray matter)

  • Simultaneous multisite recordings combined with behavior test & Optogenetic
In Vitro
NEUROSAFETY PACKAGE:
EFFECT OF COMPOUND ON CNS PROPERTIES

Hippocampal slice from WT rats or mice

  • Basal synaptic transmission
  • Short-termsynaptic plasticity (PPF)
  • Long-termsynaptic plasticity (LTP)

Cerebellum slice from WT rats or mice

  • Spontaneous firing
PRO-CONVULSIVE PACKAGE:
EVALUATION OF COMPOUND SEIZUROGENIC OR PRO-CONVULSIVE PROPERTIES

Hippocampal slice from WT rat

  • Epileptiform Discharges (ED)
  • Population Spike (PS) shape
  • CA1 neurons firing
HUMAN PERIPHERAL NEUROPATHY

Human DRG

  • Calcium Imaging: Sensitization of Electrical Field
    Stimulation-induced responses
  • Sensitization of TRPV1 / TRPA1
In Vivo
SIDE EFFECT OF ANTIPSYCHOTICS

Mice

  • Catalepsy: bar test
Keep
in touch