Language

English

Publication Date

1-1-2024

Journal

Current Neuropharmacology

DOI

10.2174/1570159X22666240530095721

PMID

38919004

PMCID

PMC11451319

PubMedCentral® Posted Date

6-24-2024

PubMedCentral® Full Text Version

Post-print

Abstract

Background: Excessive free radicals are implicated in the pathophysiology of tardive dyskinesia (TD), and Ginkgo biloba extract (EGb761) scavenges free radicals, thereby enhancing antioxidant enzymes such as mitochondrial manganese superoxide dismutase (MnSOD). This study examined whether EGb761 treatment would improve TD symptoms and increase MnSOD activity, particularly in TD patients with specific MnSOD Val-9Ala genotype.

Methods: An EGb761 (240 mg/day) 12-week double-blind clinical trial with 157 TD patients was randomized. The severity of TD was measured by the Abnormal Involuntary Movement Scale (AIMS) and plasma MnSOD activity was assayed before and after 12 weeks of treatment. Further, in an expanded sample, we compared MnSOD activity in 159 TD, 227 non-TD and 280 healthy controls, as well as the allele frequencies and genotypes for the MnSOD Ala-9Val polymorphism in 352 TD, 486 non-TD and 1150 healthy controls.

Results: EGb761 significantly reduced TD symptoms and increased MnSOD activity in TD patients compared to placebo (both p < 0.01). Moreover, we found an interaction between genotype and treatment response (p < 0.001). Furthermore, in the EGb761 group, patients carrying the Ala allele displayed a significantly lower AIMS total score than patients with the Val/Val genotype. In addition, MnSOD activity was significantly lower at baseline in TD patients compared with healthy controls or non-TD patients.

Conclusion: EGb761 treatment enhanced low MnSOD activity in TD patients and produced greater improvement in TD symptoms in patients with the Ala allele of the MnSOD Ala-9Val polymorphism.

Keywords

Adult, Aged, Female, Humans, Male, Middle Aged, Double-Blind Method, Genotype, Ginkgo biloba, Plant Extracts, Superoxide Dismutase, Tardive Dyskinesia, Treatment Outcome, Schizophrenia, genotype, pharmacogenetics, ginkgo biloba extract, tardive dyskinesia, plasma MnSOD

Comments

Clinical Trial Registration No: NCT00672373.

Published Open-Access

yes

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