Abstract
HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neurodegenerative disease of the central nervous system induced by human T-lymphotropic virus type 1. As a potential therapeutic approach, we previously suggested reducing the proviral load by modulating lysine deacetylase activity using valproic acid (VPA) and exposing virus-positive cells to the host immune response. We conducted a single-center, 2-year, open-label trial, with 19 HAM/TSP volunteers treated with oral VPA. Proviral load, CD38/HLA-DR expression, and CD8(+) lysis efficiency were not significantly affected by VPA. Mean scores of HAM/TSP disability did not differ between baseline and final visit. Walking Time Test increased significantly (> 20%) in 3 patients and was in keeping with minor VPA side effects (drowsiness and tremor). Walking Time Test improved rapidly after VPA discontinuation. We conclude that long-term treatment with VPA is safe in HAM/TSP.
Publication types
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Controlled Clinical Trial
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Aged
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CD4-Positive T-Lymphocytes / drug effects
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CD4-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / drug effects
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CD8-Positive T-Lymphocytes / metabolism
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Cytophagocytosis / drug effects
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Enzyme Inhibitors / administration & dosage
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Enzyme Inhibitors / adverse effects*
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Enzyme Inhibitors / therapeutic use
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Female
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Human T-lymphotropic virus 1 / drug effects
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Humans
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Immunity, Cellular / drug effects
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Lymphocyte Activation / drug effects
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Male
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Middle Aged
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Paraparesis, Tropical Spastic / blood
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Paraparesis, Tropical Spastic / drug therapy*
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Paraparesis, Tropical Spastic / immunology*
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Paraparesis, Tropical Spastic / virology
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Proviruses / drug effects
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Severity of Illness Index
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T-Lymphocytes, Cytotoxic / drug effects
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T-Lymphocytes, Cytotoxic / immunology
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Time Factors
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Valproic Acid / administration & dosage
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Valproic Acid / adverse effects*
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Valproic Acid / therapeutic use
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Viral Load / drug effects
Substances
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Enzyme Inhibitors
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Valproic Acid