Effects of Montelukast on Neuroinflammation in Parkinson's Disease: An Open Label Safety and Tolerability Trial with CSF Markers and [¹¹C]PBR28 PET.

IF 7.4 1区医学 Q1 CLINICAL NEUROLOGY Movement Disorders Pub Date : 2025-02-06 DOI:10.1002/mds.30144

Johan Wallin, Anton Forsberg, Per Svenningsson

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引用次数: 0

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.

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来源期刊

Movement Disorders 医学-临床神经学

CiteScore

13.30

自引率

8.10%

发文量

371

审稿时长

12 months

期刊介绍： Movement Disorders publishes a variety of content types including Reviews, Viewpoints, Full Length Articles, Historical Reports, Brief Reports, and Letters. The journal considers original manuscripts on topics related to the diagnosis, therapeutics, pharmacology, biochemistry, physiology, etiology, genetics, and epidemiology of movement disorders. Appropriate topics include Parkinsonism, Chorea, Tremors, Dystonia, Myoclonus, Tics, Tardive Dyskinesia, Spasticity, and Ataxia.