Nakamura Tatsufumi, Nishiura Yoshihiro, Eguchi Katsumi
Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, Japan.
Cent Nerv Syst Agents Med Chem. 2009 Jun;9(2):137-49. doi: 10.2174/187152409788452090.
Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is chronic progressive myelopathy characterized by bilateral pyramidal tracts involvement with sphincteric disturbances. HTLV-I infects approximately 10-20 million people worldwide. There are large endemic areas in southern Japan, the Caribbean, Central and South America, the Middle East, Melanesia, and equatorial regions of Africa. Since the primary neuropathological feature of HAM/TSP is chronic inflammation caused by HTLV-I infection in the spinal cord, various treatments focusing on immunomodulatory or anti-viral effects were performed for HAM/TSP patients until now. However, there are still many of problems, such as insufficient effects, side effects and expensive costs in long-term treatments, etc., in these treatments. Therefore, an ideal therapeutic strategy against HAM/TSP is still not established yet. Although only a small proportion of HTLV-I-infected individuals develops HAM/TSP, neurological symptoms are certainly progressive once myelopathy develops, leading to deterioration of the quality of life. Therefore, we now need the therapeutic regimens to protect the development, or be able to commence the treatments as soon as possible after the development safely and inexpensively even in long-term course or lifelong course of treatment. As HTLV-I-infected CD4(+) T cells are the first responders in the immunopathogenesis of HAM/TSP, the ideal treatment is the elimination of HTLV-I-infected cells from the peripheral blood. In this article, we will review the therapeutic strategies against HAM/TSP up to now and will introduce our new therapeutic approach focusing on the targeting of HTLV-I-infected cells in HAM/TSP patients.
人类嗜T淋巴细胞病毒I型（HTLV-I）相关脊髓病/热带痉挛性截瘫（HAM/TSP）是一种慢性进行性脊髓病，其特征为双侧锥体束受累并伴有括约肌功能障碍。HTLV-I在全球感染了约1000万至2000万人。在日本南部、加勒比地区、中南美洲、中东、美拉尼西亚和非洲赤道地区存在大片流行区。由于HAM/TSP的主要神经病理学特征是脊髓中HTLV-I感染引起的慢性炎症，迄今为止，针对HAM/TSP患者进行了各种侧重于免疫调节或抗病毒作用的治疗。然而，这些治疗仍存在许多问题，如疗效不足、副作用以及长期治疗费用昂贵等。因此，针对HAM/TSP的理想治疗策略尚未确立。虽然只有一小部分HTLV-I感染者会发展为HAM/TSP，但一旦脊髓病发展，神经症状肯定会逐渐加重，导致生活质量下降。因此，我们现在需要治疗方案来预防其发展，或者即使在长期或终身治疗过程中，也能够在发病后尽快安全且廉价地开始治疗。由于HTLV-I感染的CD4(+) T细胞是HAM/TSP免疫发病机制中的首要应答细胞，理想的治疗方法是从外周血中清除HTLV-I感染的细胞。在本文中，我们将回顾迄今为止针对HAM/TSP的治疗策略，并介绍我们针对HAM/TSP患者中HTLV-I感染细胞靶向治疗的新方法。
