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01-06-2014

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

Authors: Tatsufumi Nakamura, Katsuya Satoh, Taku Fukuda, Ikuo Kinoshita, Yoshihiro Nishiura, Kunihiko Nagasato, Atsushi Yamauchi, Yasufumi Kataoka, Tadahiro Nakamura, Hitoshi Sasaki, Kenji Kumagai, Masami Niwa, Mitsuru Noguchi, Hideki Nakamura, Noriyuki Nishida, Atsushi Kawakami

Published in: Journal of NeuroVirology | Issue 3/2014

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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Title: Pentosan polysulfate treatment ameliorates motor function with increased serum soluble vascular cell adhesion molecule-1 in HTLV-1-associated neurologic disease
Authors: Tatsufumi Nakamura
Katsuya Satoh
Taku Fukuda
Ikuo Kinoshita
Yoshihiro Nishiura
Kunihiko Nagasato
Atsushi Yamauchi
Yasufumi Kataoka
Tadahiro Nakamura
Hitoshi Sasaki
Kenji Kumagai
Masami Niwa
Mitsuru Noguchi
Hideki Nakamura
Noriyuki Nishida
Atsushi Kawakami
Publication date: 01-06-2014
Publisher: Springer US
Published in: Journal of NeuroVirology / Issue 3/2014
Print ISSN: 1355-0284
Electronic ISSN: 1538-2443
DOI: https://doi.org/10.1007/s13365-014-0244-8

At a glance: The STEP trials

Springer Medicine

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

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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