Pushing the Boundaries of Parkinson’s Disease Research – Together with Roche
Orally Bioavailable Dopamine D1/D5 Receptor-Biased Agonist to Study the Role of β‑Arrestin in Treatment-Related Dyskinesia in Parkinson’s Disease
In Brief (3 Key Points)
- Compound 24, developed with Roche, shows strong efficacy in reducing BetaPark oscillations (linked to motor symptoms in PD).
- It limits GammaPark oscillations, reducing the risk of dyskinesia compared to conventional L-DOPA treatment.
- SynapCell’s EEG biomarker platform accelerates the evaluation of CNS drug candidates, supporting safer and longer-lasting therapies.
A strategic collaboration between SynapCell and Roche
We’re excited to share the promising results of our collaboration with F. Hoffmann-La Roche AG, marking a significant step forward in the fight against Parkinson’s Disease (PD) and treatment-induced dyskinesia.
Methodology and preclinical model
Using SynapCell’s validated rat model of L-DOPA-induced dyskinesia, enhanced with EEG recordings, Roche’s compound 24 demonstrated robust and sustained efficacy in reducing BetaPark oscillations — a translational EEG biomarker closely linked to motor symptoms in PD.
Key findings of the study on compound 24
Reduction of BetaPark Oscillations
What makes this particularly exciting? Even at low doses, compound 24 significantly reduced BetaPark activity while limiting the emergence of GammaPark oscillations, the biomarker associated with dyskinesia. This dual action offers a clear advantage over conventional L-DOPA treatment.
Clinical impact and therapeutic advantages
These findings highlight the potential of compound 24, a D1/D5 receptor G protein-biased agonist with significant β-arrestin recruitment, as a safer, longer-lasting alternative to current PD therapies.
Perspectives for research and development
At SynapCell, we combine translational EEG biomarkers with behavioral endpoints to deliver a powerful, clinically relevant platform for evaluating CNS drug candidates — empowering our partners to accelerate decision-making and drug development.
Comparative data: compound 24, tavapadon, and L-DOPA
Acute treatment with compound 24 at 0.3−3 mg/kg po (red) and tavapadon at 2−8 mg/kg po (blue) on EEG biomarkers (over a 60 min
period) in the rat LID model, showing that both compounds (A) reduced beta power indicating efficacy and (B) increased gamma power indicating dyskinesia, with similar effects as the reference compound L-DOPA (gray). (C) Compound 24 and tavapadon have longer duration of action than LDOPA, as shown by representative individual EEG time−frequency plots highlighting gamma (γ) and beta (β) power bands. (D, E) On the behavior readout (total AIM score), L-DOPA, compound 24, and tavapadon induced dyskinesia compared to the vehicle. Compound 24 (0.3 and 1 mg/kg) at 45 and 90 min (D) and tavapadon (2 mg/kg) at 60 min (E) had a significantly lower dyskinesia score compared with L-DOPA. Data are expressed as means± SEM (n = 14−16, crossover design) with individual values (circles in (A) and (B)). Dunnett’s post hoc test: ##p < 0.01, ###p < 0.001 compared with the vehicle; *p < 0.05, **p < 0.01, and ***p < 0.001 compared with L-DOPA (at the same time point in (D) and (E)).e 20 min epochs beginning 10 min after treatment administration.
A significant step forward in the development of safer, longer-lasting treatments for Parkinson’s Disease, highlighting the power of collaboration between SynapCell and Roche.