Reduced Prevalence of Parkinson's Disease in Patients Prescribed Calcineurin Inhibitors.

Autor:	Silva JD; Department of Neurology, Mitchell Center for Neurodegenerative Disorders, University of Texas Medical Branch, Galveston, TX, USA.; Pharmacology and Toxicology Graduate Program, University of Texas Medical Branch, Galveston, TX, USA., Jupiter DC; Department of Biostatistics and Data Science, University of Texas Medical Branch, Galveston, TX, USA.; Department of Orthopaedics and Rehabilitation, University of Texas Medical Branch, Galveston, TX, USA., Taglialatela G; Department of Neurology, Mitchell Center for Neurodegenerative Disorders, University of Texas Medical Branch, Galveston, TX, USA.
Jazyk:	angličtina
Zdroj:	Journal of Parkinson's disease [J Parkinsons Dis] 2024; Vol. 14 (3), pp. 533-543.
DOI:	10.3233/JPD-230313
Abstrakt:	Background: Preclinical evidence suggests calcineurin inhibitors (CNIs) combat α-synuclein-induced neuronal dysfunction and motor impairments. However, whether CNIs prevent or treat Parkinson's disease (PD) in humans has never been investigated. Objective: We seek to ascertain if prescription of CNIs is linked to a decreased prevalence of PD in a varied patient population and to glimpse into the mechanism(s) and target site through which CNIs might decrease PD prevalence. Methods: We analyzed electronic health records (EHRs) from patients prescribed the brain penetrant CNI tacrolimus (TAC), the peripherally restricted CNI cyclosporine (CySp), or the non-CNI sirolimus (SIR). For comparison, EHRs from a diverse population from the same network served as a general population-like control. After propensity-score matching, prevalence, odds, and hazards of PD diagnoses among these cohorts were compared. Results: Patients prescribed CNIs have decreased odds of PD diagnosis compared to the general population-like control, while patients prescribed SIR do not. Notably, patients prescribed TAC have a decreased prevalence of PD compared to patients prescribed SIR or CySp. Conclusions: Our results suggest CNIs, especially those acting within the brain, may prevent PD. The reduced prevalence of PD in patients prescribed TAC, compared to patients prescribed SIR, suggests that mechanisms of calcineurin inhibition- other than immunosuppression, which is common to both drugs- are driving the reduction. Therefore, CNIs may provide a promising therapeutic approach for PD.
Databáze:	MEDLINE
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