Exploring the neuroprotective potential of immunosuppressants in Parkinson's disease

Authors

Huiam M. Mubarak, Department of Neurology, Barrow Neurological Institute, 240 W Thomas Rd, Phoenix, AZ, 85013, USA. Electronic address: Huiam.Mubarak@barrowneuro.org.
Brad A. Racette, Department of Neurology, Barrow Neurological Institute, 240 W Thomas Rd, Phoenix, AZ, 85013, USA; Department of Neurology, Washington University School of Medicine in St. Louis, 660 S Euclid Ave, St. Louis, MO, 63110, USA; School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, 27 St Andrews Rd, Parktown, 2193, South Africa. Electronic address: Brad.Racette@barrowneuro.org.
Jordan A. Killion, Department of Neurology, Barrow Neurological Institute, 240 W Thomas Rd, Phoenix, AZ, 85013, USA. Electronic address: Jordan.Killion@barrowneuro.org.
Irene M. Faust, Department of Neurology, Barrow Neurological Institute, 240 W Thomas Rd, Phoenix, AZ, 85013, USA. Electronic address: Irene.Faust@barrowneuro.org.
Osvaldo J. Laurido-Soto, Department of Neurology, Washington University School of Medicine in St. Louis, 660 S Euclid Ave, St. Louis, MO, 63110, USA. Electronic address: ojlaurido-soto@wustl.edu.
Sai Anmisha Doddamreddy, Department of Neurology, Barrow Neurological Institute, 240 W Thomas Rd, Phoenix, AZ, 85013, USA. Electronic address: saianmisha.doddamreddy@barrowneuro.org.
Susan Searles Nielsen, Department of Neurology, Washington University School of Medicine in St. Louis, 660 S Euclid Ave, St. Louis, MO, 63110, USA. Electronic address: snielsen@wustl.edu.

Document Type

Article

Abstract

INTRODUCTION: Neuroprotective therapy to slow Parkinson's disease (PD) progression is a critical unmet need. Neuroinflammation likely represents an important pathophysiologic mechanism for disease progression. Medications that target this inflammation, such as immunosuppressants, represent potential disease-modifying therapies for PD. The relation between these medications and PD risk might inform candidate selection. METHODS: We conducted a population-based case-control study using Medicare data from the United States. The study included 207,532 incident PD cases and 975,177 controls from 2016 to 2018, age 67-110. We examined the association between PD risk and immunosuppressant use before PD diagnosis/control selection. We considered 37 immunosuppressants, representing >10 medication classes, in Part D prescription claims. We used logistic regression to estimate the relative risk (RR) and 95 % confidence interval (CI) between each medication and PD, while accounting for age, sex, race/ethnicity, smoking, and healthcare utilization. In sensitivity analyses we applied exposure lagging, restricted to immunosuppressant users, and corrected for multiple comparisons. RESULTS: Medicare beneficiaries using the calcineurin inhibitor tacrolimus (RR 0.49, CI 0.40-0.60) and mTOR inhibitors everolimus (RR 0.38, CI 0.26-0.56) and sirolimus (RR 0.59, CI 0.37-0.93) had a lower risk of PD compared to those not taking the medication. The TNF inhibitor certolizumab was also associated with lower PD risk (RR 0.54, CI 0.34-0.84). Tacrolimus and everolimus remained significant after Bonferroni correction. Sensitivity analyses otherwise confirmed results for all four medications. CONCLUSION: Calcineurin or mTOR inhibition might reduce PD risk. Future studies should examine whether these medications or structurally similar agents might have potential as disease-modifying therapies for PD.

Medical Subject Headings

Humans; Parkinson Disease (drug therapy, epidemiology); Male; Aged; Female; Immunosuppressive Agents (pharmacology, therapeutic use); Aged, 80 and over; United States (epidemiology); Case-Control Studies; Neuroprotective Agents (pharmacology, therapeutic use); Medicare (statistics & numerical data)

Publication Date

3-1-2025

Publication Title

Parkinsonism & related disorders

E-ISSN

1873-5126

Volume

132

First Page

107294

PubMed ID

39874798

Digital Object Identifier (DOI)

10.1016/j.parkreldis.2025.107294

Recommended Citation

Mubarak, Huiam M.; Racette, Brad A.; Killion, Jordan A.; Faust, Irene M.; Laurido-Soto, Osvaldo J.; Doddamreddy, Sai Anmisha; and Searles Nielsen, Susan, "Exploring the neuroprotective potential of immunosuppressants in Parkinson's disease" (2025). Neurology. 2024.
https://scholar.barrowneuro.org/neurology/2024