Solengepras is an inhibitor of GPR6, a novel receptor found in DRD2-expressing striatal medium spiny neurons.  In the ventral striatum, these neurons play a key role in regulation of sleep and arousal.  Solengepras is designed to modulate the indirect pathway without directly targeting dopamine receptors.  In a Phase 2 trial of early Parkinson’s disease (PD), solengepras showed improvement over placebo on MDS-UPDRS Part I; here we report further investigation of the effects on non-motor symptoms.    

ASCEND was a randomized, double-blind, placebo-controlled study in early PD patients naïve to dopaminergic therapy (NCT06006247).  Participants received solengepras 150mg once daily or placebo for 12 weeks.  Post-hoc analysis of MDS-UPDRS Part I was conducted by domain using mixed model for repeated measures (MMRM). Sleep was additionally assessed with at-home EEG monitoring via the Beacon Waveband headband. 

Sixty-four participants were randomized; 63/64(98.4%) completed the treatment period.  The solengepras-treated group had an improvement in MDS-UPDRS Part I of -1.38 versus placebo (p=0.117).  Part I results were divided into 6 non-motor domains, of which sleep-related items showed the largest standardized improvement versus placebo (3 items Q7,8,13; LS Mean [SE] -0.79 [0.37]), followed by pain (1 item; -0.29 [0.18]), and cognition (1 item; -0.15 [0.13]).  Thirty participants (placebo=17; solengepras=13) underwent at-home sleep assessments. Numerical improvements were observed with solengepras across several important measures of sleep architecture, including increased total sleep time versus placebo (+19.3 min [31.0]).

In this Phase 2 study in early PD, solengepras showed potential benefits in reducing non-motor symptoms, particularly in sleep-related disturbances.  At-home sleep monitoring demonstrated no overall worsening of sleep architecture and suggested a potential benefit on sleep quality. These findings support further investigation of solengepras in addressing sleep disturbance in PD.