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: Reza Boostani, Rosita Vakili, Samane Sadat Hosseiny, Ali Shoeibi, Bahare Fazeli, Mohammad Mehdi Etemadi, Faeze Sabet, Narges Valizade, Seyed Abdolrahim Rezaee
• Journal: Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics (Neurotherapeutics) Vol. 12 Issue 4 Pg. 887-95 (Oct 2015) ISSN: 1878-7479 [Electronic] United States
• PMID: 26174324 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Basic-Leucine Zipper Transcription Factors
• Gene Products, tax
• HBZ protein, human T-cell leukemia virus type I
• RNA, Messenger
• Retroviridae Proteins
• Vanadates
• Interferons
• Prednisolone

Topics

• Adult
• Anti-Inflammatory Agents (pharmacology, therapeutic use)
• Basic-Leucine Zipper Transcription Factors (metabolism)
• Cross-Sectional Studies
• Disability Evaluation
• Female
• Gene Expression Regulation, Viral (drug effects)
• Gene Products, tax (metabolism)
• Humans
• Interferons (pharmacology, therapeutic use)
• Leukocytes, Mononuclear (drug effects)
• Male
• Middle Aged
• Paraparesis, Tropical Spastic (complications, drug therapy, etiology, pathology, virology)
• Prednisolone (pharmacology, therapeutic use)
• RNA, Messenger (metabolism)
• Retroviridae Proteins (metabolism)
• Vanadates (pharmacology, therapeutic use)
• Young Adult