HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP): Still an Obscure Disease

Micheli      Mainardi Pillat; Moises      Evandro Bauer; Augusto      Cesar Penalva de Oliveira; Henning      Ulrich; Jorge      Casseb

Abstract

Human T-cell leukemia virus type 1 (HTLV-1) is the ethiologic agent of the neurological disorder HTLV-1- associated myelopathy/tropical spastic paraparesis (HAM/TSP). Although the majority of HTLV-1-infected individuals remain asymptomatic during their lifetime, approximately one percent of this population develops a myelopathy consisting of a chronic inflammation of the white and gray matter of the spinal cord. Glucocorticoids are widely used for treatment because of their anti-inflammatory properties, improving symptoms mainly in those patients with only a few years from onset of the disease, when inflammation is more prominent. Interferon-alpha and vitamin C are other therapies presenting some benefits in clinical practice, probably due to their anti-viral and immunomodulatory activities observed ex vivo. Furthermore, inhibitors of histone deacetylase, which increase virus expression but result in a substantial decline in the proviral load, have also been proposed. This review is intended to bridge the gap between clinical and basic science by presenting recent findings on HAM/TSP disease, mechanisms of drug action, and benefits of these therapies in HAM/TSP patients.

Keywords: HTLV-1, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), glucocorticoids, neuroinflammation, pathogenesis, HAM/TSP therapy, Interferon-alpha and vitamin C, T-cell leukemia/lymphoma (ATL), inflammatory disorders, vasopressin, angiotensin, pharmacology