Session Time: 1:45pm-3:15pm
Location: Agora 3 West, Level 3
Objective: To evaluate the Levodopa induced dyskinesia (LID) in the clinical view point of autophagy and cellular energy homeostasis, and the pharmacological effect of adenosine A2A receptor antagonist (Istradefylline; IST) adjunct to L-dopa (IST-Ld).
Background: Striatal cellular energy homeostasis are maintained by protein kinase of adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. A2AR antagonist have the non-canonical effects to regulate AMPK signalings.
Method: The study was approved by the local ethics committee of our hospital, and informed consent were obtained from the patients. The cohort recruited 62 patients with early to advanced stages of PD as part of open-label trials for five years from 2013 to 2018. Effects of the IST-Ld were prospectively measured with Clinical Global Impression-Global Improvement Scale (CGI-I), and the Unified Parkinson’s Disease Rating Scale (UPDRS), and Unified Dyskinesia Rating Scale (UDysRS). The biomarkers of autophagy functions were measured; body weight changes (⊿), blood levels of Insulin/ICG-1 and transferrin. The levels of p-α-synclein of plasma (IMR) were measured in severe dyskinesia patients. Wilcoxon signed-rank test and binomial logistic regression analysis were used with IBM SPSS statistics version 12.0.
Results: The frequency of dyskinesia; baseline, 26.1%; 36 months, 39.6%, 60 months 33.3%. The significant odds ratio of the genesis of dyskinesia; ⊿body weight, UPDRS part 3 score, and blood biomarkers of autophagy (p<0.05).
Conclusion: IST-Ld did not promote the genesis of dyskinesia, which may be both the possibility of the L-dopa sparing effect of IST and the suppression of L-dopa induced aberrant downscaling of autophagy and energy metabolism.
References: 1) N kanzato. Branched chain amino acid (BCAA) and cellular metabolism. –alternative therapy for tardive extrapyramidal disorders-. Seishinka 2019, 34(1),1-5.
To cite this abstract in AMA style:NAO. Kanzato. Pharmacological effect of adenosine A2A receptor antagonist for levodopa-induced dyskinesia associated with cellular energy homeostasis [abstract]. Mov Disord. 2019; 34 (suppl 2). https://www.mdsabstracts.org/abstract/pharmacological-effect-of-adenosine-a2a-receptor-antagonist-for-levodopa-induced-dyskinesia-associated-with-cellular-energy-homeostasis/. Accessed December 1, 2023.
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