New Parkinson Disease Biomarker Provides Opportunity for Drug Development

Yann Roche, PhD, chief innovation officer, SynapCell

Yann Roche, PhD

This week, SynapCell and Motac Neuroscience jointly announced their discovery of a novel biomarker of disease progression in Parkinson disease, named BetaPark [evo], data on which was presented at the Society for Neuroscience Annual Meeting in Chicago, Illinois.

Expected to be commercially available for pharmaceutical use in preclinical drug discovery by the second quarter of 2020, the companies stated that the biomarker “enables unprecedented opportunities for drug developers to test the neuroprotective or disease-modifying effects of their compounds.” In the 12-week research assessment of the biomarker, data showed a correlation between substantia nigra neuronal loss and an increase in BetaPark power in an animal model. Additionally, when exposed to levodopa treatment, the animals showed a statistically significant decrease of BetaPark power, confirming the pharmacosensitivity of the biomarker.

To learn more about this discovery and what the implications are for the treatment of Parkinson disease, NeurologyLive spoke to Yann Roche, PhD, chief innovation officer, SynapCell.

NeurologyLive: What led to the discovery of this new biomarker?

Yann Roche, PhD: This discovery is the result of a 2-year partnership with Motac Neuroscience, a brain focused preclinical CRO, in which scientific operations are led by a KOL in Parkinson disease: Dr Erwan Bezard.

Motac was able to provide an alpha-synuclein AAV construct to SynapCell to model a rat model of Parkinson disease progression. SynapCell has extensive experience in modeling and characterizing brain disorders using electroencephalographic (EEG) measures on translational rodent models. The company identifies disease-specific EEG patterns out of the brain of the animal models to assess investigational drug compounds efficacy in vivo. An effective drug candidate is expected to silence such abnormal brain oscillations.

Since 2015, SynapCell has made available a model and biomarker of symptomatic Parkinson, used by pharmaceutical companies to evaluate the anti-Parkinson disease and anti-dyskinetic effect of investigational compounds. The alpha-synuclein model has been phenotyped by SynapCell to investigate whether it was expressing a biomarker of Parkinson disease and if this biomarker was progressively rising as the disease was progressing.

What prompted research into BetaPark [evo]?

No translational biomarker of Parkinson disease progression exists to date. Novel therapeutic strategies look into means to lower or prevent disease progression through disease-modifying treatments.

What do clinicians need to know about BetaPark [evo]?

Beta oscillations have widely been characterized in the clinic and clinical research on Parkinson patients. Prominent beta oscillations are involved in motor deficits—movement initiation in Parkinson disease—and are considered as the most reliable biomarker of Parkinson disease to date. BetaPark is the brand name for beta oscillations at SynapCell. BetaPark [evo] corresponds to the brand name for beta oscillations identified in the alpha-synuclein rat model.

With EEG readouts being similar between human patients and animal models, we propose that beta oscillations should be used as a primary readout for parkinsonism and BetaPark [evo] as the first biomarker of Parkinson disease progression.

What has the data shown so far?

Data showed that beta oscillations are found in human patients, symptomatic preclinical models of Parkinson disease, and on models of early stages of Parkinson disease. More importantly, the BetaPark [evo] biomarker identified by SynapCell correlates to neuron loss in a brain region affected by Parkinson disease, the substantia nigra.

It was also demonstrated that BetaPark intensity was progressing in the same direction as neuron loss, making it a reliable biomarker of disease progression. in this context, BetaPark was rebranded BetaPark [evo] for evolutive Parkinson disease.

Are there further plans to validate for clinical use?

Our clients are pharmaceutical companies developing drugs for patients. SynapCell offers preclinical drug efficacy validation using animal models. Since EEG highly translates from human to rodent and from rodent to human, SynapCell’s approach is predictive.

Data obtained from SynapCell enable drug developers to predict the in-human effect of their investigational compounds and get Go/No-Go validation criteria for their drug candidates so they can secure their development phases.

Transcript edited for clarity.

REFERENCE

SynapCell and Motac Neuroscience Discover New Biomarker of Parkinson’s Disease Progression [press release]. Chicago, IL: SynapCell and Motac Neuroscience; Published October 21, 2019. news.decresearch.com/synapcell-motac-neuroscience-discover-new-biomarker-parkinsons-disease-progression. Accessed October 22, 2019.