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Pentosan polysulfate treatment ameliorates motor function with increased serum soluble vascular cell adhesion molecule-1 in HTLV-1-associated neurologic disease

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Abstract

The main therapeutic strategy against human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) characterized by lower extremity motor dysfunction is immunomodulatory treatment, with drugs such as corticosteroid hormone and interferon-α, at present. However, there are many issues in long-term treatment with these drugs, such as insufficient effects and various side effects. We now urgently need to develop other therapeutic strategies. The heparinoid, pentosan polysulfate sodium (PPS), has been safely used in Europe for the past 50 years as a thrombosis prophylaxis and for the treatment of phlebitis. We conducted a clinical trial to test the effect of subcutaneous administration of PPS in 12 patients with HAM/TSP in an open-labeled design. There was a marked improvement in lower extremity motor function, based on reduced spasticity, such as a reduced time required for walking 10 m and descending a flight of stairs. There were no significant changes in HTLV-I proviral copy numbers in peripheral blood contrary to the inhibitory effect of PPS in vitro for intercellular spread of HTLV-I. However, serum soluble vascular cell adhesion molecule (sVCAM)-1 was significantly increased without significant changes of serum level of chemokines (CXCL10 and CCL2). There was a positive correlation between increased sVCAM-1and reduced time required for walking 10 m. PPS might induce neurological improvement by inhibition of chronic inflammation in the spinal cord, through blocking the adhesion cascade by increasing serum sVCAM-1, in addition to rheological improvement of the microcirculation. PPS has the potential to be a new therapeutic tool for HAM/TSP.

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Acknowledgement

We thank Prof. Akio Adachi of the University of Tokushima Graduate School for providing H9/K30 luc cells. We also thank the other members of the Pentosan Study Group at Nagasaki University for their suggestions at research discussions regarding the style of translational research. We are grateful to H. Benend (bene GmbH, Munich, Germany) for supplying the pentosan polysulfate SP 54 ampules and Tadashi Matsumoto (ReqMed Co., Ltd., Tokyo, Japan) for the assistance in planning this study. We would also like to acknowledge the nurses who supported this work and Kaori Furukawa for providing excellent technical assistance. This study was supported by a grant from the feasibility study stage of the Japan Science and Technology Agency (JST) (grant number AS2211341G) and partially supported by the Health and Labour Sciences Research Grant on Intractable Diseases (Neuroimmunological Diseases) from the Ministry of Health, Labour and Welfare of Japan.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan

    Tatsufumi Nakamura, Katsuya Satoh & Noriyuki Nishida

  2. Translational Medicine Unit, Department of Clinical Neuroscience and Neurology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

    Taku Fukuda, Hideki Nakamura & Atsushi Kawakami

  3. Neurology Section, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki, Japan

    Ikuo Kinoshita

  4. Neurology Section, Isahaya Health Insurance General Hospital, Nagasaki, Japan

    Yoshihiro Nishiura & Kunihiko Nagasato

  5. Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan

    Atsushi Yamauchi & Yasufumi Kataoka

  6. Department of Hospital Pharmacy, Nagasaki University Hospital, Nagasaki, Japan

    Tadahiro Nakamura & Hitoshi Sasaki

  7. Orthopaedic Surgery Section, Ekisaikai Hospital, Nagasaki, Japan

    Kenji Kumagai

  8. Department of Pharmacology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan

    Masami Niwa

  9. Department of Urology, Saga University Faculty of Medicine, Saga, Japan

    Mitsuru Noguchi

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  1. Tatsufumi Nakamura
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  2. Katsuya Satoh
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  3. Taku Fukuda
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  5. Yoshihiro Nishiura
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  6. Kunihiko Nagasato
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  8. Yasufumi Kataoka
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  9. Tadahiro Nakamura
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  10. Hitoshi Sasaki
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  11. Kenji Kumagai
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  12. Masami Niwa
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  13. Mitsuru Noguchi
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  14. Hideki Nakamura
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  15. Noriyuki Nishida
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  16. Atsushi Kawakami
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Correspondence to Tatsufumi Nakamura.

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Nakamura, T., Satoh, K., Fukuda, T. et al. Pentosan polysulfate treatment ameliorates motor function with increased serum soluble vascular cell adhesion molecule-1 in HTLV-1-associated neurologic disease. J. Neurovirol. 20, 269–277 (2014). https://doi.org/10.1007/s13365-014-0244-8

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