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First published online January 1, 2011

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.

References

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Article first published online: January 1, 2011
Issue published: January 2011

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Authors

Affiliations

Natsumi Araya
Department of Molecular Medical Science, Institute of Medical Science, St Marianna University School of Medicine, Kawasaki, Japan
Katsunori Takahashi
Department of Molecular Medical Science, Institute of Medical Science, St Marianna University School of Medicine, Kawasaki, Japan
Tomoo Sato
Department of Molecular Medical Science, Institute of Medical Science, St Marianna University School of Medicine, Kawasaki, Japan
Tatsufumi Nakamura
Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
Chika Sawa
Department of Molecular Medical Science, Institute of Medical Science, St Marianna University School of Medicine, Kawasaki, Japan
Daisuke Hasegawa
Department of Molecular Medical Science, Institute of Medical Science, St Marianna University School of Medicine, Kawasaki, Japan
Hitoshi Ando
Department of Molecular Medical Science, Institute of Medical Science, St Marianna University School of Medicine, Kawasaki, Japan
Satoko Aratani
Department of Molecular Medical Science, Institute of Medical Science, St Marianna University School of Medicine, Kawasaki, Japan
Naoko Yagishita
Department of Molecular Medical Science, Institute of Medical Science, St Marianna University School of Medicine, Kawasaki, Japan
Ryoji Fujii
Department of Molecular Medical Science, Institute of Medical Science, St Marianna University School of Medicine, Kawasaki, Japan
Hiroshi Oka
Department of Molecular Medical Science, Institute of Medical Science, St Marianna University School of Medicine, Kawasaki, Japan
Kusuki Nishioka
Institute of Innovative Medical Science and Education, Tokyo Medical University, Tokyo, Japan
Toshihiro Nakajima
Institute of Innovative Medical Science and Education, Tokyo Medical University, Tokyo, Japan
Naoki Mori
Division of Molecular Virology and Oncology, Graduate School of Medicine, University of Ryukyus, Nishihara, Okinawa, Japan
Yoshihisa Yamano
Department of Molecular Medical Science, Institute of Medical Science, St Marianna University School of Medicine, Kawasaki, Japan

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