Effects of Montelukast on Neuroinflammation in Parkinson's Disease: An Open Label Safety and Tolerability Trial with CSF Markers and [11C]PBR28 PET.
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Wallin J, Forsberg A, Svenningsson P
Mov Disord 40 (4) 739-744 [2025-04-00; online 2025-02-06]
Dysregulated leukotriene signaling is proposed to be involved in pathogenesis of Parkinson's disease (PD). 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. 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), [11C]PBR28-PET, and lumbar punctures before and during montelukast treatment. 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. [11C]PBR28 binding was lowered in high, but not mixed, affinity binders after montelukast. 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.
Swedish Metabolomics Centre [Service]
PubMed 39912596
DOI 10.1002/mds.30144
Crossref 10.1002/mds.30144