Boston – December 5, 2025 – While the prevalence of Parkinson’s disease (PD) has doubled over the past 20 years, the treatment paradigm has remained largely unchanged. In fact, for more than fifty years, the management of PD has centered on dopamine replacement therapy. Despite the profound emotional and physiological impact of the disease, current treatments provide only incremental relief. Innovative thinking and new therapeutic tools are urgently needed to better improve patient outcomes.
Understanding the Realities of Today’s PD Treatment Paradigm
Despite major advances in neuroscience, PD treatment has seen limited true innovation since levodopa’s approval in 1967. Dopaminergic therapies remain the cornerstone of symptom management, but over time, dose and frequency of treatment need to be increased, creating significant need for millions of patients worldwide.
As PD advances, the brain's ability to store and release dopamine diminishes, leading to "wearing off" and "on-off" fluctuations between doses. For many, these fluctuations can mean alternating between periods of mobility and immobility several times a day. Side effects such as dyskinesia and hallucinations often compound these challenges, underscoring the limitations of dopamine-centric strategies.
Most symptomatic treatments for PD today, and those in development, focus on reformulating or re-engineering dopamine-based therapies. These efforts may improve convenience, but they don’t address the fundamental pharmacological ceiling of the dopamine pathway. Cerevance is taking a different approach.
A Paradigm Shift: Identifying GPR6
At Cerevance, we asked a foundational question: Can motor function be improved without replacing or mimicking dopamine?
This led us to the identification of GPR6, a previously unexplored receptor that offers the potential to rebalance brain signaling in PD without engaging the dopamine system. This non-dopaminergic approach targets the brain circuitry involved in PD in a fundamentally new approach.
Identifying GPR6 led us to develop solengepras, a novel and highly selective GPR6 inhibitor capable of crossing the blood-brain barrier. It is designed to normalize overactivity in brain pathways that contribute directly to motor symptoms, offering the potential to reduce OFF time, the challenging periods when PD symptoms suddenly return and impair daily functioning. This represents a meaningful advancement, as over 90% of people with PD experience at least one daily OFF episode, and even modest improvements can significantly enhance quality of life. Additionally, solengepras demonstrates a more favorable tolerability profile compared with traditional dopaminergic therapies. In a Phase 2 adjunctive study in individuals with PD experiencing motor fluctuations, once-daily oral solengepras achieved a statistically significant reduction in average daily OFF time compared to placebo after only 27 days of treatment.
When applying a regulatory-standardized analysis to a subset of patients with three or more hours of baseline OFF time (approximately 90% of study participants), the reduction in daily OFF time was reduced by 1.78 hours. This effect is comparable to results achieved in other clinical studies with continuous dopaminergic infusion therapies, but with a well-tolerated, non-invasive oral regimen.
These results validate GPR6 as a promising new target for PD and demonstrate that a non-dopaminergic mechanism can deliver clinically meaningful improvements for patients.
Advancing This Novel Non-Dopaminergic Therapy
Building on the positive Phase 2 results, we launched ARISE, a global Phase 3 adjunctive study evaluating solengepras in individuals with PD. The study is designed to demonstrate solengepras’ potential to reduce OFF time, improve non-motor symptoms, and deliver consistent benefit without the tolerability tradeoffs seen with dopamine-based therapy.
A New Era in PD Therapeutics
As the PD population continues to grow—it’s projected to reach more than 25 million people globally by 2050—the need for innovative, non-dopaminergic strategies has never been clearer.
By pursuing a novel mechanism with strong clinical validation and leveraging a human-first discovery approach, solengepras has the potential to lead the next major evolution in PD care. The goal is simple: to provide a new therapeutic option that works alongside current standards, reduces unpredictability, and gives patients more consistent control over their daily lives.
With Phase 3 data expected in 2026, solengepras may soon demonstrate whether targeting GPR6 can truly redefine what’s possible in PD treatment.
Written by Mark Carlton, Chief Scientific Officer, Cerevance
About Cerevance
Cerevance is focused on advancing cell type-specific therapies for the treatment of neurodegenerative diseases and obesity. Our proprietary platform, Nuclear Enriched Transcript Sort sequencing (NETSseq), allows us to identify targets that are expressed at very low levels, that are present in rare cell types, or that change over time as a disease progresses. Our most advanced investigational treatment, solengepras, is currently in Phase 3 development and has the potential to be a first-in-class, oral non-dopaminergic therapy for both motor and non-motor symptoms of Parkinson's disease. Our second investigational treatment, CVN293, is a highly selective investigational oral inhibitor targeting potassium two pore domain channel subfamily K member 13 (KCNK13). CVN293 represents a potentially novel intervention point for neurodegenerative disorders and obesity.
For more information, please visit www.cerevance.com and follow us on LinkedIn and X.
###
Contacts
Cerevance:
Johnna Simoes, ir@cerevance.com
Media
April Dovorany, adovorany@realchemistry.com
