@article{oai:nagasaki-u.repo.nii.ac.jp:00016829,
 author = {Nishiura, Yoshihiro and Nakamura, Tatsufumi and Fukushima, Naomi and Nakamura, Hideki and Ida, Hiroaki and Aramaki, Toshiyuki and Eguchi, Katsumi},
 issue = {4},
 journal = {Antiviral therapy},
 month = {},
 note = {BACKGROUND: This study was conducted to construct a basis for a therapeutic strategy against human T-lymphotropic virus type-I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) using a compound that contained a disulfide moiety, prosultiamine, which is a homologue of allithiamine originally synthesized by allicin and thiamine-thiol, for the targeting of HTLV-I-infected cells. METHODS: First, we analysed the apoptotic pathway in allicin or prosultiamine treatment against an HTLV-I-infected T-cell line (HCT-1), derived from an HAM/TSP patient, by flow cytometry and western blot. Second, we evaluated the effect of targeting HTLV-I-infected cells in a prosultiamine in vitro treatment and in a clinical trial in HAM/TSP patients by quantitative PCR analysis of HTLV-I proviral load. RESULTS: Prosultiamine, like allicin, induced caspase-dependent apoptosis against HCT-1 cells. The fact that the loss of mitochondrial membrane potential was recovered in z-VAD-fmk-pretreated HCT-1 cells with prosultiamine treatment suggested that prosultiamine can induce caspase-dependent apoptosis through the mitochondrial pathway. On the basis of data showing that prosultiamine in vitro treatment against peripheral blood CD4(+) T-cells of HAM/TSP patients induced a significant decrease of HTLV-I proviral copy numbers by apoptosis of HTLV-I-infected cells, we treated six HAM/TSP patients with intravenous administration of prosultiamine for 14 days. As a result of this treatment, the copy numbers of HTLV-I provirus in peripheral blood decreased to approximately 30-50% of their pretreatment levels with some clinical benefits in all patients. CONCLUSIONS: Our results suggest that prosultiamine has the potential to be a new therapeutic tool that targets HTLV-I-infected cells in HAM/TSP., Antiviral therapy, 14(4), pp.533-542; 2009},
 pages = {533--542},
 title = {Disulfide-mediated apoptosis of human T-lymphotrophc virus type-I (HTLV-I)-infected cells in patients with HTLV-I-associated myelopathy/tropical spastic paraparesis.},
 volume = {14},
 year = {2009}
}