title: Pentosan polysulfate treatment ameliorates motor function with increased serum soluble vascular cell adhesion molecule-1 in HTLV-1-associated neurologic disease.
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.
authors.affiliation: Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan, tatsu@nagasaki-u.ac.jp.
authors.forename: Tatsufumi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Katsuya
authors.initials: K
authors.lastname: Satoh
authors.forename: Taku
authors.initials: T
authors.lastname: Fukuda
authors.forename: Ikuo
authors.initials: I
authors.lastname: Kinoshita
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Nishiura
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Nagasato
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yamauchi
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Kataoka
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Nakamura
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sasaki
authors.forename: Kenji
authors.initials: K
authors.lastname: Kumagai
authors.forename: Masami
authors.initials: M
authors.lastname: Niwa
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Noguchi
authors.forename: Hideki
authors.initials: H
authors.lastname: Nakamura
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Nishida
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kawakami
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects; D020805:Central Nervous System Viral Diseases / Q000188:drug therapy*; D018932:Chemokine CCL2 / Q000097:blood; D054357:Chemokine CXCL10 / Q000097:blood; D005260:Female; D015490:HTLV-I Infections / Q000188:drug therapy*; D015368:Human T-lymphotropic virus 1; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008875:Middle Aged; D009043:Motor Activity / Q000187:drug effects*; D010426:Pentosan Sulfuric Polyester / Q000008:administration & dosage* / Q000009:adverse effects; D012995:Solubility; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood*; D019562:Viral Load / Q000187:drug effects; D016138:Walking
chemical_list: D000925:Anticoagulants; C111835:CCL2 protein, human; C114753:CXCL10 protein, human; D018932:Chemokine CCL2; D054357:Chemokine CXCL10; D019010:Vascular Cell Adhesion Molecule-1; D010426:Pentosan Sulfuric Polyester