Objective: To evaluate the effect of selnoflast, an NLRP3 inhibitor, in persons with early-stage Parkinson’s disease (PD).

Background: Damage-associated molecular patterns and pathological alpha-synuclein from damaged or dying neurons activate NLRP3 inflammasomes, triggering abnormal microglial responses, inflammasome markers and neuroinflammation, contributing to PD progression and neurodegeneration.

Method: A total of 57 people with early-stage PD (modified Hoehn & Yahr Stage 1−2.5, treatment-naïve or on stable symptomatic therapy, with confirmed abnormal dopaminergic imaging) participated in a 4-week, Phase Ib study to evaluate the safety, pharmacokinetics, and pharmacodynamics of selnoflast (200 mg twice daily) (Figure 1).

Results: Baseline characteristics (Table 1) and adverse event profiles (Table 2) were largely similar between the 39 selnoflast-treated participants and the 18 participants on placebo. Selnoflast showed a favorable safety and tolerability profile, with no serious adverse events, dose interruptions, or treatment withdrawals reported. The PK profile for selnoflast was in line with expectations, achieving high occupancy in the CNS. Evidence of peripheral and central target engagement on NLRP3-related biomarkers was recorded. Selnoflast drove a >90% inhibition of ex vivo IL-1β release, a 57.6% adjusted mean decrease in plasma hsCRP, and a 30.1% adjusted mean decrease in CSF IL-18. Additionally, TSPO-PET imaging showed clear pharmacodynamic effects on microglia in key affected brain regions, including the midbrain and putamen. Results regarding IL-6 and other biomarkers will be presented at this congress.

Conclusion: The observed effect on peripheral and central NLRP3-related biomarkers and pharmacodynamic effect on key regions of the brain reinforces NLRP3 inhibition support the continued investigation of NLRP3 inhibition as potential therapeutic target in PD. 

This abstract was previously presented at ADPD 2026 on 18 March 2026.

Table 1

Table 2

Figure 1

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MDS Abstracts - https://www.mdsabstracts.org/abstract/nlrp3-inhibition-in-early-stage-parkinsons-disease-results-of-a-phase-ib-study/