Longer Duration of MAO-B Inhibitor Exposure is Associated with Less Clinical Decline in Parkinson's Disease: An Analysis of NET-PD LS1.

Autor: Hauser RA; Departments of Neurology, Molecular Pharmacology and Physiology, University of South Florida, Parkinson's Disease and Movement Disorders Center, National Parkinson Foundation Center of Excellence, Tampa FL, USA., Li R; Department of Biostatistics, The University of Texas Health Science Center at Houston (UTHealth) School of Public Health, Houston, TX, USA., Pérez A; Department of Biostatistics, The University of Texas Health Science Center at Houston (UTHealth) School of Public Health, Houston, TX, USA., Ren X; Department of Biostatistics, The University of Texas Health Science Center at Houston (UTHealth) School of Public Health, Houston, TX, USA., Weintraub D; Departments of Psychiatry and Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA., Elm J; Medical University of South Carolina, Department of Public Health Sciences, Charleston, SC, USA., Goudreau JL; Department of Neurology, Michigan State University, East Lansing, MI, USA., Morgan JC; National Parkinson Foundation Center of Excellence, Movement Disorders Program, Department of Neurology, Medical College of Georgia, Augusta University, Augusta, GA, USA., Fang JY; Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA., Aminoff MJ; University of California, San Francisco, Department of Neurology, University of California, San Francisco, CA, USA., Christine CW; University of California, San Francisco, Department of Neurology, University of California, San Francisco, CA, USA., Dhall R; The Parkinson's Institute and Clinical Center, Sunnyvale, CA, USA., Umeh CC; Division of Movement Disorders, Brigham and Women's Hospital, Boston, MA, USA., Boyd JT; Department of Neurological Sciences, University of Vermont, College of Medicine, Burlington, VT, USA., Stover N; Department of Neurology, The University of Alabama at Birmingham, Birmingham, AL, USA., Leehey M; Department of Neurology, University of Colorado, School of Medicine, Aurora, CO, USA., Zweig RM; Department of Neurology, Louisiana State University Health Sciences Center in Shreveport, Shreveport, LA, USA., Nicholas AP; Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, USA., Bodis-Wollner I; Departments of Neurology and Ophthalmology, Parkinson's Disease and Related Disorders Clinic, Center of Excellence, State University of New York, Downstate Medical Center, Brooklyn, NY, USA., Willis A; Department of Neurology, The University of Pennsylvania School of Medicine, Philadelphia, PA, USA., Kieburtz K; University of Rochester, Center for Human Experimental Therapeutics, Rochester, NY, USA., Tilley BC; Department of Biostatistics, The University of Texas Health Science Center at Houston (UTHealth) School of Public Health, Houston, TX, USA.
Jazyk: angličtina
Zdroj: Journal of Parkinson's disease [J Parkinsons Dis] 2017; Vol. 7 (1), pp. 117-127.
DOI: 10.3233/JPD-160965
Abstrakt: Background: Monoamine oxidase type B (MAO-B) inhibitors exhibit neuroprotective effects in preclinical models of PD but clinical trials have failed to convincingly demonstrate disease modifying benefits in PD patients.
Objective: To perform a secondary analysis of NET-PD LS1 to determine if longer duration of MAO-B inhibitor exposure was associated with less clinical decline.
Methods: The primary outcome measure was the Global Outcome (GO), comprised of 5 measures: change from baseline in the Schwab and England (ADL) scale, the 39-item Parkinson's Disease Questionnaire (PDQ-39), the UPDRS Ambulatory Capacity Scale, the Symbol Digit Modalities Test, and the most recent Modified Rankin Scale. A linear mixed model was used to explore the association between the cumulative duration of MAO-B inhibitor exposure and the GO, adjusting for necessary factors and confounders. Associations between MAO-B inhibitor exposure and each of the five GO components were then studied individually.
Results: 1616 participants comprised the analytic sample. Mean observation was 4.1 (SD = 1.4) years, and 784 (48.5%) participants received an MAO-B inhibitor. The regression coefficient of cumulative duration of MAO-B inhibitor exposure (in years) on the GO was - 0.0064 (SE = 0.002, p = 0.001). Significant associations between duration of MAO-B inhibitor exposure and less progression were observed for ADL (p < 0.001), Ambulatory Capacity (p < 0.001), and the Rankin (p = 0.002).
Conclusions: Our analysis identified a significant association between longer duration of MAO-B inhibitor exposure and less clinical decline. These findings support the possibility that MAO-B inhibitors slow clinical disease progression and suggest that a definitive prospective trial should be considered.
Databáze: MEDLINE
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