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

Boostani, R. and Vakili, R. and Hosseiny, S. S. and Shoeibi, A. and Fazeli, B. and Etemadi, M. M. and Sabet, F. and Valizade, N. and Rezaee, S. A. (2015) 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. Neurotherapeutics, 12 (4). pp. 887-895.

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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/104 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. © 2015, The American Society for Experimental NeuroTherapeutics, Inc.

Item Type: Article
Additional Information: Cited By :12 Export Date: 16 February 2020 Correspondence Address: Rezaee, S.A.; Inflammation and Inflammatory Diseases Research Center, Faculty of Medicine, Mashhad University of Medical SciencesIran; email: rezaeer@mums.ac.ir
Uncontrolled Keywords: clinical symptoms combination therapy HAM/TSP HBZ HTLV-1 proviral load Tax messenger RNA peginterferon prednisolone valproic acid antiinflammatory agent basic leucine zipper transcription factor HBZ protein, human T-cell leukemia virus type I interferon Tax protein vanadic acid viral protein adult antibody response antibody titer Article Ashworth spasticity scale clinical article demography female gene gene expression HBZ gene human Human T-lymphotropic virus 1 low back pain male micturition motor dysfunction assessment Osame Motor Disability Score peripheral blood mononuclear cell pollakisuria priority journal real time polymerase chain reaction spasticity tax gene treatment outcome tropical spastic paraparesis urine incontinence virus load young adult complication cross-sectional study disability drug effects gene expression regulation metabolism middle aged mononuclear cell Paraparesis, Tropical Spastic pathology virology Anti-Inflammatory Agents Basic-Leucine Zipper Transcription Factors Cross-Sectional Studies Disability Evaluation Gene Expression Regulation, Viral Gene Products, tax Humans Interferons Leukocytes, Mononuclear Retroviridae Proteins RNA, Messenger Vanadates
Subjects: QV pharmacology
QZ pathology-neoplasms-Genetics
Divisions: Mashhad University of Medical Sciences
Depositing User: mr lib5 lib5
Date Deposited: 12 May 2020 05:55
Last Modified: 12 May 2020 05:55
URI: http://eprints.mums.ac.ir/id/eprint/18801

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