Disease-Modifying Effect of Zonisamide with the Induction of BDNF and TrkB Expression

(Background)　Zonisamide reduced the nigrostriatal doperminergic neurodegeneration in a mouse model of PD with chronic administration through BDNF increase in the striatum and ventral midbrain.

(Objective)To evaluate the predictors of the disease-modifying effect of drugs of 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.

(Material and Methods)The study was approved by the local ethics committee of our hospital and informed
consent were obtained from the patients.
A total of 387 PD patients visiting our clinic over a period of 10 years (2006-2016) were reviewed based on their medical records. Serum BDNF (QuantikineR 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.

(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). 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. Serum BDNF was lower in PD with a long duration, although PD with Zonisamide showed no difference compared with the normal control.

(Conclusion) Long-term therapy with Zonisamide may be the possible for DM-PD induced by epigenetic modification.