[Developing novel treatments for HTLV-1-associated myelopathy (HAM) by investigating molecular pathomechanisms]

Nihon Rinsho Meneki Gakkai Kaishi. 2016;39(3):207-12. doi: 10.2177/jsci.39.207.
[Article in Japanese]

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.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / therapeutic use*
  • Astrocytes
  • Chemokine CXCL10 / immunology
  • Clinical Trials as Topic
  • Feedback, Physiological / physiology
  • Humans
  • Molecular Targeted Therapy*
  • Paraparesis, Tropical Spastic / drug therapy*
  • Paraparesis, Tropical Spastic / etiology*
  • Receptor Cross-Talk / physiology
  • Receptors, CCR4 / immunology*
  • Receptors, CXCR3 / immunology
  • T-Lymphocytes*
  • Th1 Cells

Substances

  • Antibodies, Monoclonal
  • CXCL10 protein, human
  • CXCR3 protein, human
  • Chemokine CXCL10
  • Receptors, CCR4
  • Receptors, CXCR3