학술논문

Developing novel treatments for HTLV-1-associated myelopathy (HAM) by investigating molecular pathomechanisms / HTLV-1関連脊髄症(HAM)の分子病態解明による治療薬開発の新展開
Document Type
Journal Article
Source
日本臨床免疫学会会誌 / Japanese Journal of Clinical Immunology. 2016, 39(3):207
Subject
CCR4
CXCL10
CXCR3
HAM
astrocyte
Language
Japanese
ISSN
0911-4300
1349-7413
Abstract
A small percentage of those infected with human T-lymphotropic virus type 1 (HTLV-1) develop HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a debilitating neurodegenerative disease. This disease impacts essential bodily functions, and since currently available treatments are considered to be poorly effective, there is a dire need to develop a truly effective treatment to suppress disease progression. Recently, the authors and others have determined that HTLV-1 in HAM/TSP patients primarily infects T cells expressing the chemokine receptor CCR4. The authors postulated that HTLV-1 causes these T cells to develop Th1-like functions that are critical for the pathogenesis of HAM/TSP. They described an inflammatory positive feedback loop in which cross-talk between these abnormal Th1-like cells and astrocytes produce and maintain spinal cord lesions in HAM/TSP patients. When an anti-CCR4 antibody was tested against cells from HAM/TSP patients, the antibody instigated the destruction of the CCR4-positive cells, reducing the number of infected cells and the amount of inflammatory activity. Thus, the anti-CCR4 antibody is expected to become a fundamentally new treatment for HAM/TSP that directly targets infected cells. The treatment is currently being tested in clinical trials.