Efficacy of a novel drug, zonisamide, in the modulation of oxidative stress in Parkinson's disease

Background Urinary 8‐hydroxy‐2′‐deoxyguanosine is frequently used as an index of cytotoxicity, particularly for oxidative stress. Current research shows that urinary 8‐hydroxy‐2′‐deoxyguanosine levels increase with age, disease duration and severity in patients with Parkinson's disease. In particular, a previous study reported that 8‐hydroxy‐2′‐deoxyguanosine levels were increased in patients with hallucinations. Aim Urinary 8‐hydroxy‐2′‐deoxyguanosine levels were investigated as an indicator of clinical progression of Parkinson's disease. Urinary 8‐hydroxy‐2′‐deoxyguanosine was examined in association with oxidative stress, in addition to modification by drug administration. Methods We recruited 122 patients with Parkinson's disease (mean age 66.9 ± 7.9 years; severity [Hoehn and Yahr scale] 2.2 ± 0.9). Data obtained from 73 patients who underwent long‐term analysis of urinary 8‐hydroxy‐2′‐deoxyguanosine levels for at least two consecutive years were used for longitudinal analysis. Changes in urinary 8‐hydroxy‐2′‐deoxyguanosine levels were used as a disease biomarker, while Hoehn and Yahr stage was used as an indicator of severity. Results Baseline urinary 8‐hydroxy‐2′‐deoxyguanosine levels were found to significantly correlate with age at examination, Hoehn and Yahr stage, scores on the total Unified Parkinson's Disease Rating Scale, and part 1.2 (hallucinations). In patients received dopamine agonists, changes in Hoehn and Yahr stage and urinary 8‐hydroxy‐2′‐deoxyguanosine were significant over 1 year, indicating a worsening of pathology. In zonisamide‐treated patients, urinary 8‐hydroxy‐2′‐deoxyguanosine levels usually decreased. Conclusion In Parkinson's disease patients, oxidative stress correlates with disease progression. As studies suggest zonisamide inhibits neuronal cell death, our results support a possible role for zonisamide in the suppression of oxidative stress in Parkinson's disease.