objectivE MEASURES OF MOTOR ABNORMALITIES
High frequencies bands from the motor cortex are strongly related to long-term L-DOPA induced dyskinesia.
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 standard for treating PD patients.
After an initial “honeymoon” period when L-DOPA almost completely reversed the signs and symptoms of Parkinson’s disease, the treatment 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.
Treatment with dopamine agonists induces a rise of GammaPark expression.
used to behavior monitoring?
- 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.
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.
example: effect of amantadine on lid
- 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.
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