SynapCell

L-DOPA-INDUCED DYSKINESIA, GAMMAPARK

objectivE MEASURES OF MOTOR ABNORMALITIES

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

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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.
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GAMMA-OHDA-SynapCell-In-vivo-efficacy-Testing-on-CNS-disorders

Treatment with dopamine agonists induces a rise of GammaPark expression.

used to behavior monitoring?

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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, longitudinally, using GammaPark modulation as a metric.
  • Find out the most effective dose of your compound in a dynamic fashion.
  • Get the pharmacodynamic signature of your compound effect with GammaPark.
  • Amantadine dose-dependently lowers L-DOPA induced GammaPark intensity over time.
  • L-DOPA induced dyskinesia (AIM scoring) are reduced by an increasing dose of Amantadine.
  • GammaPark and dyskinesia are both lowered by Amantadine.
  • GammaPark therefore represents an objective means to address L-DOPA induced dyskinesia within the motor cortex and is particularly well-suited to evaluate the effect of add-on therapies over chronic L-DOPA treatment.

example: effect of amantadine on lid

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