Service de Neurologie, Centre Hospitalier Universitaire de Fort-de-France, Martinique, France.
Blood. 2011 Dec 8;118(24):6306-9. doi: 10.1182/blood-2011-04-349910. Epub 2011 Oct 13.
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.
人类 T 淋巴细胞病毒 1 型相关性脊髓病/热带痉挛性截瘫（HAM/TSP）是一种由人类 T 淋巴细胞病毒 1 型引起的中枢神经系统退行性疾病。我们之前提出，通过使用丙戊酸钠（VPA）调节赖氨酸去乙酰化酶活性并使病毒阳性细胞暴露于宿主免疫反应，可能会降低前病毒载量，作为一种潜在的治疗方法。我们进行了一项为期 2 年、单中心、开放性试验，19 名 HAM/TSP 志愿者接受了口服 VPA 治疗。VPA 对前病毒载量、CD38/HLA-DR 表达和 CD8(+)裂解效率没有显著影响。HAM/TSP 残疾的平均评分在基线和最后一次就诊时没有差异。3 名患者的行走时间测试显著增加（>20%），并与 VPA 的轻微副作用（嗜睡和震颤）一致。VPA 停药后行走时间测试迅速改善。我们的结论是，长期使用 VPA 治疗 HAM/TSP 是安全的。
