Objective: To assess safety and tolerability of high dose Montelukast as a possible disease modifying treatment for Parkinson’s disease.

Background: Emerging evidence suggests that the innate and adaptive immune system plays a large role in disease progression in PD.¹ Specifically, dysregulated leukotriene signaling is proposed to be involved in the pathology of α-synucleinopathies.² Montelukast is a cysteinyl-leukotriene receptor 1 antagonist approved for the treatment of asthma in children and adults.

Method: 15 PD patients (7 male and 8 female) were recruited to a 12-week open-label trial to assess safety and tolerability of 20 mg bi-daily montelukast treatment. Patients were assessed at baseline, 4, and 12 weeks. Primary outcome was adverse events. Secondary outcomes were MDS-UPDRS, MoCA, BDI, PDQ-39, plasma, and CSF concentrations of montelukast.

Results: No patient discontinued the study prematurely. The study drug was well tolerated with few reported adverse events. Three patients experienced loose stool but not severe enough to affect quality of life or motivate a reduction of the medication. One patient experienced worsening of tremor during the study which motivated a reduction of the study medication and the symptoms resolved after.

12 weeks after start of treatment, scores in MDS-UPDRS part 1 had improved with 2.3 points (95 % CI 1.1 to 3.5, p= 0.001), scores in MDS-UPDRS part 2 had improved with 1.7 points (95 % CI 0.4 to 2.9, p = 0.013) and scores in MDS-UPDRS part 3 had improved with 2.9 points (95 CI 0.59 to 5.28, p = 0.018). A statistically significant improvement in scores was also observed in BDI and MoCA. No significant changes were observed in PDQ-39.

Average plasma concentrations of montelukast after 4 weeks of treatment was 1621.26 ng/ml (± 361.11). Average CSF concentrations of montelukast after 4 weeks of treatment was 3.66 (± 1.31) ng/ml. No montelukast was detected in baseline plasma or CSF samples.

Conclusion: High dose montelukast is well tolerated in PD patients. Montelukast is confirmed to cross the blood-brain barrier making the CNS a possible treatment target. Improvements in clinical scores suggest a possible effect of montelukast in symptomatic treatment of PD warranting further clinical trials.

References: 1. Tansey MG, Wallings RL, Houser MC, Herrick MK, Keating CE, Joers V. Inflammation and immune dysfunction in Parkinson disease. Nat Rev Immunol 2022;22(11):657-673.
2. Strempfl K, Unger MS, Flunkert S, et al. Leukotriene Signaling as a Target in alpha;-Synucleinopathies. Biomolecules 2022;12(3):346.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/montelukast-as-disease-modifying-treatment-for-parkinsons-disease-a-pilot-study/