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

Robert A Hauser; Ruosha Li; Adriana Pérez; Xuehan Ren; Dan Weintraub; Jordan Elm; John L Goudreau; John C Morgan; John Y Fang; Michael J Aminoff; Chadwick W Christine; Rohit Dhall; Chizoba C Umeh; James T Boyd; Natividad Stover; Maureen Leehey; Richard M Zweig; Anthony P Nicholas; Ivan Bodis-Wollner; Allison Willis; Karl Kieburtz; Barbara C Tilley; NINDS NET-PD Investigators

doi:10.3233/JPD-160965

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

J Parkinsons Dis. 2017;7(1):117-127. doi: 10.3233/JPD-160965.

Authors

Robert A Hauser¹, Ruosha Li², Adriana Pérez², Xuehan Ren², Dan Weintraub³, Jordan Elm⁴, John L Goudreau⁵, John C Morgan⁶, John Y Fang⁷, Michael J Aminoff⁸, Chadwick W Christine⁸, Rohit Dhall⁹, Chizoba C Umeh¹⁰, James T Boyd¹¹, Natividad Stover¹², Maureen Leehey¹³, Richard M Zweig¹⁴, Anthony P Nicholas¹⁵, Ivan Bodis-Wollner¹⁶, Allison Willis¹⁷, Karl Kieburtz¹⁸, Barbara C Tilley²; NINDS NET-PD Investigators

Affiliations

¹ 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.
² Department of Biostatistics, The University of Texas Health Science Center at Houston (UTHealth) School of Public Health, Houston, TX, USA.
³ Departments of Psychiatry and Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
⁴ Medical University of South Carolina, Department of Public Health Sciences, Charleston, SC, USA.
⁵ Department of Neurology, Michigan State University, East Lansing, MI, USA.
⁶ National Parkinson Foundation Center of Excellence, Movement Disorders Program, Department of Neurology, Medical College of Georgia, Augusta University, Augusta, GA, USA.
⁷ Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA.
⁸ University of California, San Francisco, Department of Neurology, University of California, San Francisco, CA, USA.
⁹ The Parkinson's Institute and Clinical Center, Sunnyvale, CA, USA.
¹⁰ Division of Movement Disorders, Brigham and Women's Hospital, Boston, MA, USA.
¹¹ Department of Neurological Sciences, University of Vermont, College of Medicine, Burlington, VT, USA.
¹² Department of Neurology, The University of Alabama at Birmingham, Birmingham, AL, USA.
¹³ Department of Neurology, University of Colorado, School of Medicine, Aurora, CO, USA.
¹⁴ Department of Neurology, Louisiana State University Health Sciences Center in Shreveport, Shreveport, LA, USA.
¹⁵ Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, USA.
¹⁶ 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.
¹⁷ Department of Neurology, The University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
¹⁸ University of Rochester, Center for Human Experimental Therapeutics, Rochester, NY, USA.

PMID: 27911341
DOI: 10.3233/JPD-160965

Abstract

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.

Keywords: MAO-B inhibitor; Parkinson’s disease; disease modification; rasagiline; selegiline; treatment.

Publication types

Multicenter Study
Randomized Controlled Trial

MeSH terms

Aged
Disease Progression*
Double-Blind Method
Female
Follow-Up Studies
Humans
Male
Middle Aged
Monoamine Oxidase Inhibitors / administration & dosage
Monoamine Oxidase Inhibitors / pharmacology*
Outcome Assessment, Health Care / methods*
Parkinson Disease / drug therapy*
Severity of Illness Index*
Time Factors

Substances

Monoamine Oxidase Inhibitors

Abstract

Publication types

MeSH terms

Substances

Grants and funding