Effects of Montelukast on Neuroinflammation in Parkinson's Disease: An Open Label Safety and Tolerability Trial with CSF Markers and [C]PBR28 PET.

BACKGROUND

Dysregulated leukotriene signaling is proposed to be involved in pathogenesis of Parkinson's disease (PD).

OBJECTIVE

The objective was to examine the safety and tolerability of montelukast, a cysteinyl-leukotriene receptor1 and GPR17 antagonist, in patients with PD. Secondary outcomes were target engagement, effects on PD signs/symptoms, and central neuroinflammation.

METHODS

Fifteen PD patients were recruited to a 12-week open-label trial of 20 mg bi-daily montelukast treatment. Patients underwent ratings with the Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS), the Montreal Cognitive Assessment (MoCA), Beck's Depression Inventory (BDI), Parkinson's Disease Questionnaire-39 (PDQ-39), [C]PBR28-PET, and lumbar punctures before and during montelukast treatment.

RESULTS

All patients completed the study. Three patients reported loose stool. No serious adverse events related to treatment were reported. MDS-UPDRS-Total scores improved by 6.9 points. Very low levels of montelukast were detected in all cerebrospinal fluid (CSF) samples and resulted in a reduction in inflammation/metabolism markers. [C]PBR28 binding was lowered in high, but not mixed, affinity binders after montelukast.

CONCLUSIONS

Montelukast crosses the blood-brain barrier at very low levels and is well tolerated and safe in PD patients. Preliminary effects on neuroinflammation and clinical scores motivate a future randomized controlled trial (RCT) in PD. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.