Developing novel treatments for HTLV-1-associated myelopathy (HAM) by investigating molecular pathomechanisms.
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.
Department of Advanced Medical Innovation, Institute of Medical Science, St. Marianna University School of Medicine.
Natsumi
N
Araya
Tomoo
T
Sato
Ariella
A
Coler-Reilly
Naoko
N
Yagishita
Yoshihisa
Y
Yamano
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001253:Astrocytes; D054357:Chemokine CXCL10 / Q000276:immunology; D002986:Clinical Trials as Topic; D025461:Feedback, Physiological / Q000502:physiology; D006801:Humans; D058990:Molecular Targeted Therapy; D015493:Paraparesis, Tropical Spastic / Q000188:drug therapy* / Q000209:etiology*; D020239:Receptor Cross-Talk / Q000502:physiology; D054398:Receptors, CCR4 / Q000276:immunology*; D054367:Receptors, CXCR3 / Q000276:immunology; D013601:T-Lymphocytes; D018417:Th1 Cells
D000911:Antibodies, Monoclonal; C114753:CXCL10 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D054398:Receptors, CCR4; D054367:Receptors, CXCR3