Safety of long-term treatment of HAM/TSP patients with valproic acid.

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.

• Authors: Stéphane Olindo, Gildas Belrose, Nicolas Gillet, Sabrina Rodriguez, Mathieu Boxus, Olivier Verlaeten, Becca Asquith, Charles Bangham, Aïssatou Signaté, Didier Smadja, Agnès Lezin, Raymond Césaire, Luc Willems
• Journal: Blood (Blood) Vol. 118 Issue 24 Pg. 6306-9 (Dec 08 2011) ISSN: 1528-0020 [Electronic] United States
• PMID: 21998206 (Publication Type: Controlled Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Valproic Acid

Topics

• Adult
• Aged
• CD4-Positive T-Lymphocytes (drug effects, metabolism)
• CD8-Positive T-Lymphocytes (drug effects, metabolism)
• Cytophagocytosis (drug effects)
• Enzyme Inhibitors (administration & dosage, adverse effects, therapeutic use)
• Female
• Human T-lymphotropic virus 1 (drug effects)
• Humans
• Immunity, Cellular (drug effects)
• Lymphocyte Activation (drug effects)
• Male
• Middle Aged
• Paraparesis, Tropical Spastic (blood, drug therapy, immunology, virology)
• Proviruses (drug effects)
• Severity of Illness Index
• T-Lymphocytes, Cytotoxic (drug effects, immunology)
• Time Factors
• Valproic Acid (administration & dosage, adverse effects, therapeutic use)
• Viral Load (drug effects)