title: Fucoidan therapy decreases the proviral load in patients with human T-lymphotropic virus type-1-associated neurological disease.
abstract: BACKGROUND
  Human T-lymphotropic virus type-1 (HTLV-1) is a human retrovirus that causes HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukaemia (ATL). A higher viral load in individuals with HTLV-1 infection increases their risk of developing HAM/TSP and ATL. Moreover, the high proviral load is associated with the clinical progression of HAM/TSP. Reduction of the number of HTLV-1-infected cells is therefore crucial for preventing and treating HTLV-1-associated diseases. Recently, fucoidan, a complex sulphated polysaccharide derived from marine seaweed, has been demonstrated to exert inhibitory effects on HTLV-1 infection in vitro. In this study, we examined the in vivo effects of fucoidan on HTLV-1 infection.
  
  
  METHODS
  In this single-centre open-label trial, 13 patients with HAM/TSP were treated with 6 g fucoidan daily for 6-13 months. The HTLV-1 proviral DNA load and frequencies of HTLV-1-specific CD8(+) T-cells, natural killer cells, invariant natural killer T-cells and dendritic cells in the peripheral blood were analysed. Furthermore, the in vitro inhibitory effect of fucoidan on cell-to-cell HTLV-1 infection was examined by using luciferase reporter cell assays.
  
  
  RESULTS
  Fucoidan inhibited the cell-to-cell transmission of HTLV-1 in vitro. Furthermore, fucoidan therapy resulted in a 42.4% decrease in the HTLV-1 proviral load without affecting the host immune cells. During the treatment, no exacerbation was observed. Four patients with HAM/TSP developed diarrhoea, which improved immediately after stopping fucoidan administration.
  
  
  CONCLUSIONS
  Fucoidan is a new potential therapeutic agent for the prevention and treatment of HTLV-1-associated diseases.
authors.affiliation: Department of Molecular Medical Science, Institute of Medical Science, St Marianna University School of Medicine, Kawasaki, Japan.
authors.forename: Natsumi
authors.initials: N
authors.lastname: Araya
authors.forename: Katsunori
authors.initials: K
authors.lastname: Takahashi
authors.forename: Tomoo
authors.initials: T
authors.lastname: Sato
authors.forename: Tatsufumi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Chika
authors.initials: C
authors.lastname: Sawa
authors.forename: Daisuke
authors.initials: D
authors.lastname: Hasegawa
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ando
authors.forename: Satoko
authors.initials: S
authors.lastname: Aratani
authors.forename: Naoko
authors.initials: N
authors.lastname: Yagishita
authors.forename: Ryoji
authors.initials: R
authors.lastname: Fujii
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Oka
authors.forename: Kusuki
authors.initials: K
authors.lastname: Nishioka
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nakajima
authors.forename: Naoki
authors.initials: N
authors.lastname: Mori
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Yamano
mesh_terms: D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002452:Cell Count; D004279:DNA, Viral / Q000032:analysis; D003713:Dendritic Cells / Q000276:immunology; D018450:Disease Progression; D005260:Female; D017930:Genes, Reporter; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000276:immunology; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D008156:Luciferases / Q000032:analysis; D008297:Male; D008875:Middle Aged; D055611:Natural Killer T-Cells / Q000276:immunology; D015493:Paraparesis, Tropical Spastic / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D011134:Polysaccharides / Q000008:administration & dosage* / Q000627:therapeutic use; D011533:Proviruses / Q000235:genetics / Q000276:immunology; D012624:Seaweed / Q000737:chemistry; D019562:Viral Load / Q000187:drug effects*
chemical_list: D004279:DNA, Viral; D011134:Polysaccharides; C007789:fucoidan; D008156:Luciferases