Abstract Details

Title Guardians of the Brain: Exploring the Neuroprotective Potential of Immunosuppressants in Parkinson Disease

Topic Movement Disorders

Presentation(s) P7 - Poster Session 7 (11:45 AM-12:45 PM)

Poster/Presentation
Number 3-009

Objective To investigate the role of immunosuppressants in Parkinson Disease (PD) risk.

Background PD is the second most common neurodegenerative disease, for which finding a neuroprotective therapy that can slow or halt progression is crucial. PD is likely multiple diseases with a common, but variable, phenotype. Nevertheless, neuroinflammation may represent a common neurodegenerative pathway and medications that target inflammation are potential disease-modifying therapies. Identifying agents with neuroprotective effects in PD has been challenging.

Design/Methods We conducted a population-based case-control study using Medicare claims data from the United States. The study included 200,437 incident PD cases and 941,727 controls from 2016-2018 and without Lewy body dementia or atypical parkinsonism. We tested the association between PD risk and immunosuppressant use during the prodromal disease period. We identified 47 immunosuppressants, representing 9 unique medication classes, in Part D prescription claims data in the 2-5 years prior to PD diagnosis/control selection. We used logistic regression to estimate the relative risk (RR) and 95% confidence interval (CI) for the relation between each medication and PD, while accounting for age, sex, race/ethnicity, smoking, and healthcare utilization.

Results Beneficiaries taking tacrolimus (RR 0.50, CI 0.40-0.61), everolimus (RR 0.35 CI 0.23-0.53), sirolimus (RR 0.59, CI 0.37-0.95), cyclosporine (RR 0.92, CI 0.74-1.14), mycophenolate (RR 0.77, CI 0.68-0.86), lenalidomide (RR 0.68, CI 0.60-0.78), or ustekinumab (RR 0.82, CI 0.56-1.22) before PD diagnosis or control selection had a lower risk of developing PD when compared to those who did not take these mediations.

Conclusions Medications from classes associated with lower risk of PD included corticosteroids, biologics, antimetabolites, and inhibitors of IMDH, JAK, MTOR, dihydrofolate reductase, and calcineurin. The medications within these classes act through mechanisms that target T cells, protein synthesis, the autophagic pathway, and their downstream effects. These medication classes might have potential as disease modifying therapies for PD.

Authors/Disclosures
Huiam Mubarak, MD (Barrow Neurological Institute) PRESENTER	Dr. Mubarak has nothing to disclose.
Osvaldo J. Laurido-Soto, MD (Washington University)	The institution of Dr. Laurido-Soto has received research support from Washington University in St. Louis.
Susan Nielsen (Washington University in St. Louis)	The institution of Susan Nielsen has received research support from National Institutes of Health. The institution of Susan Nielsen has received research support from Department of Defense. The institution of Susan Nielsen has received research support from The Michael J. Fox Foundation for Parkinson's Research. The institution of Susan Nielsen has received research support from Cure Alzheimer's. Susan Nielsen has received personal compensation in the range of $0-$499 for serving as a Panel/committee member with The Michael J. Fox Foundation for Parkinson's Research. Susan Nielsen has received personal compensation in the range of $0-$499 for serving as a Reviewer with Parkinson's Disease Foundation.
Brad A. Racette, MD, FAAN (Barrow Neurological Institute)	Dr. Racette has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for American Regent. Dr. Racette has received personal compensation in the range of $500-$4,999 for serving as a advisory council with NIEHS.

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