Category: Parkinson’s Disease: Clinical Trials
Objective: Solengepras is a GPR6-inhibitor that is being studied as an investigational treatment for Parkinson’s Disease (PD).
Background: GPR6 is a novel G-protein-coupled receptor found primarily in striatal medium spiny neurons (MSNs) of the indirect pathway. Solengepras is an oral, brain-penetrant, highly-specific GPR6-inhibitor which modulates inhibitory signaling in indirect MSNs without directly targeting dopamine or dopamine receptors. In a prior Phase 2 study in PD patients with motor fluctuations, solengepras was well-tolerated and demonstrated a clinically meaningful improvement in OFF-time with minimal dopaminergic side effects.
Method: ASCEND was a Phase 2, multi-center, randomized, double-blind, placebo-controlled study in PD patients naïve to dopaminergic therapy (NCT06006247). Participants were randomized to solengepras 150mg daily or placebo for 12 weeks. The primary efficacy endpoint was change from baseline in the MDS-UPDRS Part II+III. Secondary endpoints included individual parts of the MDS-UPDRS and measures of non-motor symptoms and quality-of-life.
Results: Sixty-four participants were enrolled and 63/64 (98.4%) completed the treatment period. While the primary endpoint Part II+III did not show a difference versus placebo (-0.73, p=0.75), solengepras demonstrated encouraging trends in functional and non-motor outcomes versus placebo, including improvements in MDS-UPDRS Part I (-1.38, p=0.12), Part II (-0.4, p=0.62), Non-Motor Symptoms Scale (-1.7, p=0.59), and Epworth Sleepiness Scale (-0.3, p=0.62). Solengepras was well-tolerated with no serious adverse events reported on study drug. Fewer adverse events related to non-motor symptoms were observed in the solengepras arm. The results are consistent with the previous Phase 2 study where solengepras demonstrated improvements in functional and non-motor symptoms in the adjunctive PD population.
Conclusion: Solengepras is an investigational GPR6-inhibitor with a novel non-dopaminergic mechanism-of-action and a favorable safety profile that may have potential benefits in functional and non-motor symptoms in both early and later stage PD.
To cite this abstract in AMA style:
S. Isaacson, K. Chou, H. Sarva, S. Merchant, C. Scholl, M. Charles, N. Brice, L. Dawson, M. Carlton, S. Vaidya, K. Kieburtz, R. Hauser, A. Ellenbogen. Solengepras: An Investigational Therapy with Potential Benefits on Functional and Non-Motor Measures in Parkinson’s Disease (PD) [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/solengepras-an-investigational-therapy-with-potential-benefits-on-functional-and-non-motor-measures-in-parkinsons-disease-pd/. Accessed November 20, 2025.« Back to 2025 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/solengepras-an-investigational-therapy-with-potential-benefits-on-functional-and-non-motor-measures-in-parkinsons-disease-pd/