L-DOPA-INDUCED DYSKINESIA

objectivE MEASURES OF MOTOR ABNORMALITIES

High frequencies bands from the motor cortex are strongly related to long-term L-DOPA induced dyskinesia.

GAMMAPRK-by-SynapCell

Our EEG capabilities enable to measure the in vivo effect of anti-dyskinetic compounds directly at the source, in the motor cortex.

Our clinically-relevant GammaPark biomarker indeed correlates to dyskinetic state in both human patients and in the unilateral 6-OHDA rat model of PD under chronic L-DOPA medication.

L-DOPA-induced dyskinesia (lid)

Levodopa (L-DOPA) is to date the gold strandard for treating PD patients.

After an initial “honeymoon” period when levodopa almost completely reversed the signs and symptoms of Parkinson’s disease, L-DOPA starts losing its effectiveness (Holford and Nutt, Eur J Clin Pharmacol. 2008) and induces motor complications.

  • Chronic L-DOPA exposure generates several side-effects such as motor complications (L-DOPA Induced Dyskinesia or LID).
  • In the translational 6-OHDA rat model of PD, L-DOPA induces a switch of EEG activities from beta (~30Hz) to gamma (~90Hz) resonant oscillations.
  • We can quantify the in vivo effect of your compound on BetaPark, on GammaPark and on AIM accurately, objectively and longitudinally.
GAMMA-OHDA-CONTROL
GAMMA-OHDA

Treatment with dopamine agonist induces a rise of GammaPark

used to behavior monitoring?

Combine GammaPark quantification with Abnormal Involuntary Movement (AIM) scoring.

Three types of AIMs can be assessed during a chronic GammaPark study:

  • Axial (Ax): contralateral torsion of the neck and body.
  • Limb (Li): involuntary and repeated movement of the contralateral forelimb.
  • Orolingual (OI): contralateral chewing, tongue sticking out.
Correlate behvioral scoring with the translational power of GammaPark in a single study. 

gammapark IS STABLE OVER TIME

  • Induced gamma oscillations (GammaPark) remain stable along the repeated treatments (5 days) with L-DOPA 20 mg/kg.
  • L-DOPA treatment in 6-OHDA rats induces a switch of EEG activities from beta (~30Hz) to gamma (~90Hz) resonant oscillations.
  • This allows for longitudinal assessment of your compound effect over several days.

USE GAMMAPARK TO BENCHMARK DIFFERENT DRUGS

  • Dopamine agonists enhance GammaPark expression.
  • Compare different drugs effects over time using GammaPark modulation.
  • Find out the dose at which your compound is the most effective.

example: effect of amantadine on lid

Choosing synapcell for your parkinson’s programs

drug-discovery-on-cns-disorders-synapcell

FEATURES

Gold standard
Stable MODEL over time
Validated by a pharmacology of reference
Quantitative

drug-discovery-on-cns-disorders-synapcell

BENEFITS

Pharmacosensitive Biomarker
Anti-parkinsonian
Anti-tremor
Anti-dystinetic

drug-discovery-on-cns-disorders-synapcell

PROGRAMS

Lead selection – validation
Dose-dependent evaluation
Parkinson’s disease
L-DOPA Induced Dyskinesia

Applications: Parkinson’s disease, Huntington’s disease, essential tremor, dyskinesia

Markers: beta and gamma oscillations, Multisite coherence

Models: 6-OHDA lesioned rats or contact us

Programs: Lead selection (screening of small libraries of compounds), lead validation (dose-response effect, pharmacokinetic), disease modifying therapeutic potential, rodent model phenotyping

Let's talk about your next project