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

IF 7.6 1区医学 Q1 CLINICAL NEUROLOGY Movement Disorders Pub Date : 2025-02-06 DOI:10.1002/mds.30144

Johan Wallin MD, Anton Forsberg PhD, Per Svenningsson PhD, MD

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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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孟鲁司特对帕金森病神经炎症的影响：CSF标志物和[11C]PBR28 PET的开放标签安全性和耐受性试验

背景：白三烯信号失调被认为参与帕金森病（PD）的发病机制。目的：目的是检查孟鲁司特（一种半胱氨酸-白三烯受体1和GPR17拮抗剂）在PD患者中的安全性和耐受性。次要结局是靶标参与、PD体征/症状的影响和中枢神经炎症。方法：招募15名PD患者，进行为期12周的开放标签试验，每天服用20mg孟鲁司特治疗。患者在孟鲁司特治疗前和治疗期间分别采用运动障碍学会统一帕金森病评定量表（MDS-UPDRS）、蒙特利尔认知评估（MoCA）、贝克抑郁量表（BDI）、帕金森病问卷-39 （PDQ-39）、[11C]PBR28-PET和腰椎穿刺进行评分。结果：所有患者均完成了研究。3例患者报告大便疏松。未见与治疗相关的严重不良事件报告。mds - updrs -总分提高6.9分。在所有脑脊液（CSF）样本中检测到极低水平的孟鲁司特，导致炎症/代谢标志物减少。[11C]使用孟鲁司特后，高亲和力结合剂（而非混合亲和力结合剂）的PBR28结合降低。结论：孟鲁司特通过血脑屏障的水平非常低，在PD患者中具有良好的耐受性和安全性。对神经炎症和临床评分的初步影响激发了PD的未来随机对照试验（RCT）。©2025作者。Wiley期刊有限责任公司代表国际帕金森和运动障碍学会出版的《运动障碍》。

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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.