Effects of Montelukast on Neuroinflammation in Parkinson's Disease: An Open Label Safety and Tolerability Trial with <scp>CSF</scp> Markers and [<scp><sup>11</sup>C</scp>]<scp>PBR28 PET</scp>
Movement Disorders, 2025
Wallin J., Forsberg A., Svenningsson P.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Neurology | Pathophysiology | Plasma CSF | O Olink Target 96 |
Abstract
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), [11C]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. [11C]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.