Abstract
Although many experimental studies have shown the favorable effects of zonisamide on mitochondria using models of Parkinson’s disease (PD), the influence of zonisamide on metabolism in PD patients remains unclear. To assess metabolic status under zonisamide treatment in PD, we performed a pilot study using a comprehensive metabolome analysis. Plasma samples were collected for at least one year from 30 patients with PD: 10 without zonisamide medication and 20 with zonisamide medication. We performed comprehensive metabolome analyses of plasma with capillary electrophoresis time-of-flight mass spectrometry and liquid chromatography time-of-flight mass spectrometry. We also measured disease severity using Hoehn and Yahr (H&Y) staging and the Unified Parkinson’s Disease Rating Scale (UPDRS) motor section, and analyzed blood chemistry. In PD with zonisamide treatment, 15 long-chain acylcarnitines (LCACs) tended to be increased, of which four (AC(12:0), AC(12:1)-1, AC(16:1), and AC(16:2)) showed statistical significance. Of these, two LCACs (AC(16:1) and AC(16:2)) were also identified by partial least squares analysis. There was no association of any LCAC with age, disease severity, levodopa daily dose, or levodopa equivalent dose. Because an upregulation of LCACs implies improvement of mitochondrial β-oxidation, zonisamide might be beneficial for mitochondrial β-oxidation, which is suppressed in PD.
Highlights
Parkinson’s disease (PD) is the second most common neurodegenerative disorder and is characterized by motor symptoms such as tremor, rigidity, and akinesia [1]
There were no significant differences in age, sex, Hoehn and Yahr (H&Y) stage, disease duration, levodopa equivalent dose (LED), or levodopa daily dose (LDD) between PD patients with or without zonisamide treatment [22]
We reported that decreased levels of long-chain acylcarnitines (LCACs) were a useful biomarker for the diagnosis of PD in a double-cohort study [15]. β-oxidation of fatty acid (FA) occurs in mitochondria and peroxisomes; β-oxidation of short-to-long-chain FAs occurs in mitochondria, whereas β-oxidation of long-chain fatty acids (LCFAs) occurs in peroxisomes
Summary
Parkinson’s disease (PD) is the second most common neurodegenerative disorder and is characterized by motor symptoms such as tremor, rigidity, and akinesia [1]. Our group previously reported the analyses of capillary electrophoresis time-of-flight mass-spectrometry (CE-TOFMS) and liquid chromatography time-of-flight mass-spectrometry (LC-TOFMS), which showed decreased long-chain acylcarnitines (LCACs) and increased long-chain fatty acids (LCFAs) in PD patients, suggesting that β-oxidation insufficiency occurs primarily in early PD, and is not associated with levodopa medication [15]. In this context, to highlight the metabolic changes that occur with zonisamide administration, we conducted a case–case study, using well-established techniques, of 20 PD patients undergoing zonisamide treatment and 10 PD patients without zonisamide treatment
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