Session Information
Date: Thursday, June 8, 2017
Session Title: Parkinson’s Disease: Clinical Trials, Pharmacology And Treatment
Session Time: 1:15pm-2:45pm
Location: Exhibit Hall C
Objective: To evaluate to predictors of the disease-modifying effect of drugs on Parkinson’s disease (DM-PD) according to long-term therapeutic investigation, especially regarding the non-dopaminergic agent Zonisamide, covered in Japan by medical insurance, and survey the biomarkers to predict DM-PD.
Background: Zonisamide reduced nigrostriatal dopaminergic neurodegenertaion in a mouse model of PD after chronic administration increasing BDNF in the striatum and ventral midbrain (Ref. J Neurochem 2015.134:371-381)
Methods: A total of 387 PD patients visiting our clinic over a period of 10 years (2006-2016) were reviewed based on their medical records. Baseline assessment factors such as the disease duration, medication history, H&Y stage (HY), and UPDRS were quantified at the last visit (including transferred or deceased cases). Serum BDNF (QuantikineR ELISA, pg/mL; USA) and TrkB (Human TRKBR sandwich ELISA, pg/mL; USA) were investigated. DNA methylations were investigated with the BDNF protein coding gene (chr11p14) , from the 5’ promotor to whole exon I and exon VI lesion. The TRKB protein coding gene (chr9q.21.33) was also investigated from the 5’ promotor to whole exon. The study was approved by the local ethics committee of our hospital,l and informed consent was obtained from each participant.
Results: About 50% of all PD patients were under HY3, being the hallmark of independency in each daily activity (HY3-DM-PD). Twenty PD patients (5.2%) were under HY3 with long disease durations (over 16 years, Fig.). Multivariate logistic analysis revealed the predictors of HY3-DM-PD, such as early onset (under 45 years), DBS- STN/GPi, and PD agents (Zonisamide and Amantadine) with significance (Table). Serum BDNF was lower in de-novo to early PD (1,450±6,960), although PD with a long duration (18,600±6,060) and PD with Zonisamide (19,150±8,156) showed no difference compared with the normal control (20,766±2,300). PD with Zonisamide showed upregulated BDNF and TrkB induced by epigenetic modification.
Conclusions: Long-term therapy with Zonisamide may be the possible for DM-PD.
To cite this abstract in AMA style:
N. Kanzato. Disease-modifying effect of Zonisamide with the induction of BDNF and TrkB expression [abstract]. Mov Disord. 2017; 32 (suppl 2). https://www.mdsabstracts.org/abstract/disease-modifying-effect-of-zonisamide-with-the-induction-of-bdnf-and-trkb-expression/. Accessed June 14, 2025.« Back to 2017 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/disease-modifying-effect-of-zonisamide-with-the-induction-of-bdnf-and-trkb-expression/