title: Triple Therapy with Prednisolone, Pegylated Interferon and Sodium Valproate Improves Clinical Outcome and Reduces Human T-Cell Leukemia Virus Type 1 (HTLV-1) Proviral Load, Tax and HBZ mRNA Expression in Patients with HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis.
abstract: Considering that there is no effective treatment for human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis, this study aimed to assess the impact of triple combination therapy-interferon-α, valproic acid, and prednisolone-on clinical outcomes, main HTLV-1 viral factors, and host anti-HTLV-1 antibody response. HTLV-1 proviral load (PVL), and HBZ and Tax mRNA expression levels were measured in peripheral blood mononuclear cells of 13 patients with HTLV-1-associated myelopathy/tropical spastic paraparesis before and after treatment with 180 μg pegylated interferon once a week, 10-20 mg/kg/day sodium valproate, and 5 mg/day prednisolone for 25 weeks using a TaqMan real-time polymerase chain reaction assay. Furthermore, anti-HTLV-1 titer, Osame Motor Disability Score, Ashworth spasticity scale, and urinary symptoms (through standard questionnaire and clinical monitoring) were assessed in patients before and after the treatment. HTLV-1 PVL and HBZ expression significantly decreased after the treatment [PVL from 1443 ± 282 to 660 ± 137 copies/10(4) peripheral blood mononuclear cells (p = 0.01); and HBZ from 8.0 ± 1.5 to 3.0 ± 0.66 (p < 0.01)]. Tax mRNA expression decreased after the treatment from 2.26 ± 0.45 to 1.44 ± 0.64, but this reduction was not statistically significant (p = 0.10). Furthermore, anti-HTLV-1 titer reduced dramatically after the treatment, from 3123 ± 395 to 815 ± 239 (p < 0.01). Clinical signs and symptoms, according to Osame Motor Disability Score and Ashworth score, improved significantly (both p < 0.01). Urinary symptoms and sensory disturbances with lower back pain were reduced, though not to a statistically significant degree. Although signs and symptoms of spasticity were improved, frequent urination and urinary incontinence were not significantly affected by the triple therapy. The results provide new insight into the complicated conditions underlying HTLV-1-associated diseases.
authors.affiliation: Department of Neurology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Boostani
authors.affiliation: Center of Pathological and Medical Diagnostic Services, Iranian Academic Center for Education, Culture & Research (ACECR), Mashhad Branch, Mashhad, Iran.
authors.forename: Rosita
authors.initials: R
authors.lastname: Vakili
authors.affiliation: Department of Biology, Science and Research Branch, Islamic Azad University, Kurdistan, Iran.
authors.forename: Samane Sadat
authors.initials: SS
authors.lastname: Hosseiny
authors.affiliation: Department of Neurology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Shoeibi
authors.affiliation: Inflammation and Inflammatory Diseases Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Bahare
authors.initials: B
authors.lastname: Fazeli
authors.affiliation: Department of Neurology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mohammad Mehdi
authors.initials: MM
authors.lastname: Etemadi
authors.affiliation: Navid Medical Lab, Mashhad, Iran.
authors.forename: Faeze
authors.initials: F
authors.lastname: Sabet
authors.affiliation: Inflammation and Inflammatory Diseases Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Narges
authors.initials: N
authors.lastname: Valizade
authors.affiliation: Inflammation and Inflammatory Diseases Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. rezaeer@mums.ac.ir.
authors.forename: Seyed Abdolrahim
authors.initials: SA
authors.lastname: Rezaee
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D050976:Basic-Leucine Zipper Transcription Factors / Q000378:metabolism*; D003430:Cross-Sectional Studies; D004185:Disability Evaluation; D005260:Female; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D016356:Gene Products, tax / Q000378:metabolism*; D006801:Humans; D007372:Interferons / Q000494:pharmacology / Q000627:therapeutic use; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D015493:Paraparesis, Tropical Spastic / Q000150:complications / Q000188:drug therapy / Q000209:etiology / Q000473:pathology / Q000821:virology; D011239:Prednisolone / Q000494:pharmacology / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism*; D012191:Retroviridae Proteins / Q000378:metabolism*; D014638:Vanadates / Q000494:pharmacology / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D050976:Basic-Leucine Zipper Transcription Factors; D016356:Gene Products, tax; C479751:HBZ protein, human T-cell leukemia virus type I; D012333:RNA, Messenger; D012191:Retroviridae Proteins; D014638:Vanadates; D007372:Interferons; D011239:Prednisolone
keywords: HAM/TSP; HBZ; HTLV-1 proviral load; Tax; clinical symptoms; combination therapy