Fucoidan therapy decreases the proviral load in patients with human T-lymphotropic virus type-1-associated neurological disease

Antivir Ther. 2011;16(1):89-98. doi: 10.3851/IMP1699.

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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Count
  • DNA, Viral / analysis
  • Dendritic Cells / immunology
  • Disease Progression
  • Female
  • Genes, Reporter
  • Human T-lymphotropic virus 1 / genetics
  • Human T-lymphotropic virus 1 / immunology
  • Humans
  • Leukemia-Lymphoma, Adult T-Cell / drug therapy*
  • Leukemia-Lymphoma, Adult T-Cell / genetics
  • Leukemia-Lymphoma, Adult T-Cell / immunology
  • Leukemia-Lymphoma, Adult T-Cell / prevention & control
  • Leukemia-Lymphoma, Adult T-Cell / virology
  • Luciferases / analysis
  • Male
  • Middle Aged
  • Natural Killer T-Cells / immunology
  • Paraparesis, Tropical Spastic / drug therapy*
  • Paraparesis, Tropical Spastic / genetics
  • Paraparesis, Tropical Spastic / immunology
  • Paraparesis, Tropical Spastic / prevention & control
  • Paraparesis, Tropical Spastic / virology
  • Polysaccharides / administration & dosage*
  • Polysaccharides / therapeutic use
  • Proviruses / genetics
  • Proviruses / immunology
  • Seaweed / chemistry
  • Viral Load / drug effects*

Substances

  • DNA, Viral
  • Polysaccharides
  • fucoidan
  • Luciferases