Precision Neurology: Redefining Parkinson’s Disease Clinical Trials

Neurological disorders affect more than 3 billion people worldwide, making them the leading cause of disability and the second leading cause of death.

In an interview with Xtalks, Craig Thompson, CEO of Cerevance, shared how the company is rethinking CNS drug discovery through its proprietary NETSseq platform to uncover novel targets and drive precision approaches in diseases like Parkinson’s and Alzheimer’s.

Despite significant investment, most neurodegenerative diseases remain without disease-modifying treatments. In fact, CNS drug development historically has a success rate below 8% from Phase I to approval, making it one of the most difficult therapeutic areas to innovate in.

“I think from the treatment perspective, we’re really lacking people going after new targets and new ways of treating disease,” Thompson explained. “We do see a lot of companies going after updated or improved versions of older drugs. And to tackle a lot of these diseases, we need to really deeply understand what is driving these diseases.”

Parkinson’s disease alone affects over 10 million people globally, while Alzheimer’s affects more than 55 million. Even with these staggering numbers, most available therapies only address symptoms rather than halting disease progression.

Another critical challenge is how progression is measured. Thompson highlighted a gap in biomarkers, which impacts how clinical trials are designed, how patients are selected and how therapies are evaluated.

“The other thing we’re also missing is really strong biomarkers, both from an ability to identify patients who are at risk as well as really looking at how patients are progressing through the disease,” he said.

Overcoming Innovation Barriers in CNS Drug Development

High attrition rates and subjective trial endpoints have long defined CNS clinical research. Unlike areas such as oncology or cardiovascular medicine, which often rely on objective lab measures, many CNS trials depend on patient-reported outcomes and clinical scales.

“If you look across the space, we still use a lot of what I would call more qualitative endpoints,” Thompson said.

“For Parkinson’s disease, for example, we use a tool called the Hauser diary… you compare that to say cardiovascular disease, where you can do a blood draw and look at your LDL level. That’s very hard evidence.”

This reliance on subjective measures increases the placebo effect and makes it harder to demonstrate drug efficacy. “If we can get more concrete blood-based biomarkers or less subjective endpoints, I think that would be really helpful both from trying to mitigate the placebo effect, but also really being able to demonstrate what a drug is doing,” he added.

Recent regulatory developments suggest progress. For example, neurofilament light chain (NfL) was accepted by the FDA as a qualified biomarker in ALS, signaling a growing willingness to incorporate biomarker-based endpoints into CNS trials.

Rethinking How to Tackle the Toughest Neurodegenerative Diseases

For Thompson, joining Cerevance was about taking a bold step rather than making incremental moves.

After years in the CNS drug development space and seeing how late-stage failures can derail progress, he wanted to lead an organization that approaches neurodegenerative diseases in a new way.

“What really attracted me to Cerevance was taking the bold move of trying to identify targets that no one else is working on by using our NETSseq platform,” Thompson said.

“I’m motivated by the chance to pursue discoveries that could have a lasting impact on patients’ lives.”

This vision reflects a pressing global need.

Millions of people worldwide live with neurological disorders, and this number is expected to rise substantially as populations age.

A Platform Built for Discovery

At the heart of Cerevance’s strategy is its NETSseq platform, which has analyzed more than 20,000 postmortem human brain tissue samples to uncover molecular changes associated with neurodegenerative diseases.

“Using human tissue, we’re able to isolate the nuclei. From those nuclei, we can capture the full transcriptome — more than 12,000 genes per cell,” Thompson explained.

Through machine learning and pseudo-time trajectory analysis, the platform identifies genes that are upregulated or downregulated over time in specific cell types, providing a detailed view of disease biology.

This strategy led to the identification of GPR6, a previously overlooked target in the brain’s indirect pathway that modulates movement in Parkinson’s disease. “Traditionally, no one had ever thought about looking for that gene,” he said. “So that gave us insight to look for something that would impact the downstream regulation of dopamine without actually impacting the dopamine pathway.”

This level of cell-type specificity sets NETSseq apart from traditional transcriptomic screening.

The Role of Biomarkers in Personalized Neurology

The field of neurology is shifting toward more personalized treatment strategies, and Cerevance is positioning itself at the forefront of this shift. Using molecular profiling, the company has identified five distinct Alzheimer’s subgroups, each with its own molecular signatures.

“We’re able to look at Alzheimer’s and we can break Alzheimer’s into what we call five different subgroups,” Thompson said. “That then allows us to look at molecules that may be targeted against those subtypes.”

By stratifying patients based on molecular characteristics, trials can become more efficient, and therapies more targeted. This approach mirrors precision medicine trends seen in oncology, applied now to neurological diseases.

Moving Beyond Dopamine in Parkinson’s

For more than 60 years, treatment for Parkinson’s disease has focused on dopaminergic therapies, which typically offer around a one hour improvement in “OFF” time. These treatments help with symptoms but do not alter disease progression and often bring significant side effects, including dyskinesia, hallucinations and cognitive impairment.

Cerevance’s lead candidate is designed as a non-dopaminergic, brain-penetrant and selective GPR6 inverse agonist aimed at improving both motor and non-motor symptoms in Parkinson’s disease.

In the Phase II adjunctive study of the lead candidate in PD patients with motor fluctuations, the drug demonstrated a statistically significant reduction of 1.3 hours (p=0.02) in average daily OFF time versus placebo after only 27 days of treatment. Further, in a supplementary post-hoc, which included the typical regulatory standardized analysis of normalizing patients to a 16-hour waking day, as well as evaluating patients with three hours or more of OFF time at baseline an even greater benefit of the lead candidate was observed, with a 1.78-hour reduction (p=0.0045) in OFF time compared to placebo at Day 27, approaching the benefits seen with invasive infusion therapies. The lead candidate was generally well tolerated with low rates of dopaminergic adverse events.

The company is currently conducting its global Phase III ARISE trial, evaluating the change in average daily “OFF” time compared to placebo. Topline results are anticipated in 2026.

Data, Patients and Real-World Impact

Cerevance’s work goes beyond clinical data. Thompson shared a personal story from an investigator meeting where he met a Parkinson’s patient.

“You start to understand why depression sets in,” he said. “They’re afraid to go out, and feel “stuck” in their own bodies — like they’ve lost their independence and the ability to move freely through their lives. So, to us, we wanted to set the bar high and achieve something that’s going to be impactful to Parkinson’s patients and make a difference in people’s lives.”

The company’s mission is as much about improving patient quality of life as it is about advancing drug development.

Driving the Next Generation of Precision Neurology

With the NETSseq platform, an extensive human brain tissue database and a growing body of biomarker and clinical data, Cerevance is working to redefine how CNS drug discovery is done.

Thompson envisions success as achieving the primary endpoint in the Phase III ARISE trial, delivering meaningful improvements in “OFF” time and showing that non-dopaminergic mechanisms can offer new hope in Parkinson’s disease.

Cerevance’s strategy reflects a pivotal shift in neurology, moving from incremental improvements toward data-driven precision discovery that targets the biological roots of disease.