Session Information
Date: Thursday, June 23, 2016
Session Title: Parkinson's disease: Clinical trials, pharmacology and treatment
Session Time: 12:00pm-1:30pm
Location: Exhibit Hall located in Hall B, Level 2
Objective: To evaluate the pharmacological properties of Adenosine A2A receptor antagonist, istradefylline (IST), and analyze A2AR protein levels of peripheral lymphocytes and the frequency of DNA methylation of the ADORA2A gene.
Methods: A total of 52 Parkinson’s disease (PD) patients with diurnal variation of motor function, 10 healthy control subjects, and 2 disease controls with tardive dyskinesia induced by antipsychiatric drugs were investigated. The study was approved by the local ehics committee of our hospital and informed consent was obtained from each participant. With the lymphocytes isolated from the peripheral blood, A2AR protein (A2AR-p) was determined by Western blotting analysis and A2AR mRNA (A2AR-m) was assayed using real-time quantitative PCR. DNA methylation in the 5’UTR region of the ADORA2A gene (22C.q11.23) was assayed by PCR, as recently described (Perez Buira S, et al. J neurochemistry 2010).
Results: Global assessments of the treatment of IST after 24 months revealed 12% marked improvement (MI), 50% slight improvement (SI), 24% no improvement (NI), 12% aggravation (A), and 6% withdrawal (WD) due to side effects of IST. A2AR-p was higher in MI compared with the patient group of A and healthy controls. A2AR-m showed no difference between the PDs and healthy controls. DNA methylation of the ADORA2A gene showed low frequencies in the patient group of MI compared with the other groups.
Conclusions: IST is effective for the off symptoms of motor dysfunction for the long-term treatment period with the adjunctive use of L-dopa and dopamine agonist. Endogenous A2AR protein levels are preferentially increased by post-transcriptional regulation, such as DNA methylation of the ADORA2A gene in PD, which influences the clinical efficacy of IST.
To cite this abstract in AMA style:
N. Kanzato, K. Nakachi, T. Naka, M. Higa, S. Mochizuki, Y. Miyamae. Efficacy of long-term treatment with istradefylline and analysis of the expression of A2A receptor protein and post-transcriptional DNA methylation [abstract]. Mov Disord. 2016; 31 (suppl 2). https://www.mdsabstracts.org/abstract/efficacy-of-long-term-treatment-with-istradefylline-and-analysis-of-the-expression-of-a2a-receptor-protein-and-post-transcriptional-dna-methylation/. Accessed September 7, 2024.« Back to 2016 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/efficacy-of-long-term-treatment-with-istradefylline-and-analysis-of-the-expression-of-a2a-receptor-protein-and-post-transcriptional-dna-methylation/