Disentangling amantadine response variability in levodopa related dyskinesias: Role of clinical and genetic factors.
Disentangling amantadine response variability in levodopa related dyskinesias: Role of clinical and genetic factors.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
Euclid, US · Author affiliation
Genomic Sciences and Systems Biology, Cleveland Clinic Research, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA; Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH, 44195, USA.Location evidence
San Antonio, US · Author affiliation
Center for Neurological Restoration, Neurological Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA; Movement Disorders Division, Department of Neurology, University of Texas Health Science Center at San Antonio, 7703 Floyrd Curl Dr, San Antonio, TX, 78229, USA.Location evidence
PH · Author affiliation · country only
Center for Neurological Restoration, Neurological Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA; Institute for Neurosciences, St. Lukes Medical Center, 5th Ave, Metro Manila, Global City, Taguig, 1634, Philippines; Cardinal Santos Medical Center, 10 Wilson, Greenhills West, Metro Manila, San Juan City, 1502, Philippines; Department of Neurosciences, University of the East, Ramon Magsaysay Memorial Medical Center, 64 Aurora Boulevard, Barangay Doña Imelda, Quezon City, 1113, Philippines.Location evidence
US · Author affiliation · country only
Center for Neurological Restoration, Neurological Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA; Institute for Neurosciences, St. Lukes Medical Center, 5th Ave, Metro Manila, Global City, Taguig, 1634, Philippines; Cardinal Santos Medical Center, 10 Wilson, Greenhills West, Metro Manila, San Juan City, 1502, Philippines; Department of Neurosciences, University of the East, Ramon Magsaysay Memorial Medical Center, 64 Aurora Boulevard, Barangay Doña Imelda, Quezon City, 1113, Philippines.Location evidence
SA · Author affiliation · country only
Center for Neurological Restoration, Neurological Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA; College of Medicine, Taibah University, Medinah, Saudi Arabia.Location evidence
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Original abstract
BACKGROUND: Amantadine is the most commonly used pharmacologic treatment for levodopa-related dyskinesias (LRD), yet its efficacy and tolerability vary substantially, challenging clinical decision-making. OBJECTIVE: To explore clinical, demographic, and genetic factors associated with variability in amantadine treatment outcomes. METHODS: Cross-sectional study of Parkinson's disease (PD) patients treated with amantadine for LRD. Participants were classified as responders or non-responders; with non-responders further subdivided according to the presence of intolerable side effects. Clinical and demographic data were collected and participants underwent genotyping. Polygenic risk scores for PD risk (PD-PRS) and genetic variants associated with levodopa or amantadine metabolism and LRD susceptibility were assessed. RESULTS: A total of 146 participants were included (male 57%, mean age 66.9 years); 94 provided biological samples and 86 passed quality control. Responders had a longer interval from PD diagnosis to amantadine initiation (median 5.5 vs. 3 years, p = 0.005) and higher levodopa equivalent daily dose (LEDD) (1057.6 mg ± 431.5 vs. 831.1 mg ± 504.7, p = 0.006). Among non-responders, LEDD was lower in those experiencing side effects (725.2 mg ± 397.5 vs. 1013.5 mg ± 613.6, p = 0.015). The DRD1 rs4532-C allele was nominally associated with favorable response, whereas ANKK1, DRD2, and COMT variants were nominally associated with side effects. PD-PRS showed no association with response. CONCLUSIONS: Clinical and genetic factors may influence amantadine response. Earlier amantadine initiation and lower LEDD were associated with a poorer response to amantadine. Genetic markers in the dopaminergic pathways may facilitate a personalized treatment approach in PD.