Therapeutic Approaches for HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis: Current and Emerging Strategies

Human T-cell leukemia virus-1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic inflammatory disease of the spinal cord induced by immunological activation due to high HTLV-1 proviral load in the peripheral blood. HAM/TSP is representative of HTLV-1-related inflammatory diseases, and its main neurological symptoms-namely, motor dysfunction of the lower extremities through spastic paraparesis with urinary disturbance-are progressive and lead to deterioration in the quality of life of patients once these dysfunctions develop. Therefore, novel and safe therapeutic regimens are needed, enabling patients to commence treatment as soon as possible after the diagnosis of HAM/TSP. To date, various treatments have been developed for the correction of the associated immunological or virological abnormalities, which have produced some good results. However, there are still many problems, such as insufficient treatment effects and side effects. In addition, most of these treatments have only been characterized in the short term, being in the open trial phase, and it remains unclear whether or not they are suitable for the long-term treatment of HAM/TSP induced by a chronic inflammatory status. Thus, we need effective therapeutic regimens with safety for long-term or even lifelong courses of treatment. In this review, we summarize the clinical trials conducted to date for various therapeutic approaches, including representative regimens against HAM/TSP, while touching on the problematic issues. In addition, we discuss several agents with the potential to enable the development of novel therapeutic regimens as emerging interventions for further investigation in future research.