Pharmacological strategies to manage oxidative stress in Huntington’s disease: from preclinical models to clinical trials
Abstract
Huntington disease (HD) is a progressive neurodegenerative disorder for which effective disease-modifying treatments remain limited. Growing evidence indicates that oxidative stress, mitochondrial dysfunction, and impaired cellular antioxidant responses are important contributors to HD pathogenesis and may interact with mechanisms that drive disease progression, including somatic CAG repeat expansion. This narrative review examines therapeutic strategies aimed at restoring redox balance in HD, with particular emphasis on approaches targeting mitochondrial function, antioxidant defense, glutathione metabolism, lipid oxidation, and metal homeostasis. Although a broad range of compounds has shown beneficial effects in experimental models, translation into clinical benefit has so far been limited. This gap may reflect insufficient target engagement, inadequate brain exposure, intervention at advanced disease stages, and the difficulty of capturing biologically meaningful effects using conventional clinical endpoints. Future therapeutic development may therefore benefit from earlier intervention, biomarker-guided patient stratification, combination strategies integrating redox modulation with huntingtin-lowering approaches, and the repurposing of clinically established drugs targeting mitochondrial and redox pathways.
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BibTeX
@article{dumala2026pharmacological,
title = {{Pharmacological strategies to manage oxidative stress in Huntington’s disease: from preclinical models to clinical trials}},
author = {Sylwester Dumała and Agata Jedrzejewska and Magdalena Kwaśniak‐Butowska and Paul A. De Sousa and Marta Tomczyk},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1984341},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1984341},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Pharmacological strategies to manage oxidative stress in Huntington’s disease: from preclinical models to clinical trials
AU - Sylwester Dumała
AU - Agata Jedrzejewska
AU - Magdalena Kwaśniak‐Butowska
AU - Paul A. De Sousa
AU - Marta Tomczyk
PY - 2026
DA - 2026/10/30
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1984341
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1984341
AB - Huntington disease (HD) is a progressive neurodegenerative disorder for which effective disease-modifying treatments remain limited. Growing evidence indicates that oxidative stress, mitochondrial dysfunction, and impaired cellular antioxidant responses are important contributors to HD pathogenesis and may interact with mechanisms that drive disease progression, including somatic CAG repeat expansion. This narrative review examines therapeutic strategies aimed at restoring redox balance in HD, with particular emphasis on approaches targeting mitochondrial function, antioxidant defense, glutathione metabolism, lipid oxidation, and metal homeostasis. Although a broad range of compounds has shown beneficial effects in experimental models, translation into clinical benefit has so far been limited. This gap may reflect insufficient target engagement, inadequate brain exposure, intervention at advanced disease stages, and the difficulty of capturing biologically meaningful effects using conventional clinical endpoints. Future therapeutic development may therefore benefit from earlier intervention, biomarker-guided patient stratification, combination strategies integrating redox modulation with huntingtin-lowering approaches, and the repurposing of clinically established drugs targeting mitochondrial and redox pathways.
SN - 1663-9812
ER -