
Administering FTY720 - an oral drug improves locomotor recovery in mice with spinal cord injury (SCI), shows study. The research suggests a possible new avenue to counteract the degeneration of the spinal cord in human SCI. The study will be published in the April 2012 issue of The American Journal of Pathology.
Beyond the initial tissue damage, much of the degradation of the spinal cord in SCI is due to a cascade of secondary injuries, including neuronal and glial apoptosis, inflammation, glial scar formation, local edema and ischemia, and oxidative stress. The aim of current SCI treatment is to counteract the mechanisms of secondary injury and prevent their pathological consequences, because central nervous system (CNS) neurons have very limited capacity to self-repair and regenerate.
Researchers from the Jichi Medical University School of Medicine and the Graduate School of Medicine at the University of Tokyo had previously shown that the concentration of the lysophospholipid mediator, sphingosine 1-phosphate (S1P), was significantly increased in the location of a contusion injury, triggering the migration of neural progenitor/stem cells to the site of the injury. They hypothesized that targeting S1P receptors may become a candidate therapy for various refractory central nervous system disorders, including SCI.
"These data clearly indicate the importance of immune-independent functions of FTY720 in the amelioration of functional deficits after SCI in mice," explains lead investigator Yoichi Sakata, MD, PhD, Research Division of Cell and Molecular Medicine, Center for Molecular Medicine, Jichi Medical University School of Medicine.
Dr. Sakata notes that S1P receptors exist in many types of cells and play a role in many cellular processes. "We observed that FTY720 decreased vascular permeability and astrocyte accumulation in injured spinal cord. These changes were also noted in SCID mice, suggesting they are not dependent on lymphocyte function. Increased vascular permeability can lead to destruction of the blood-brain barrier in spinal cord, and astrocyte accumulation is the main cellular component of glial scar after CNS injury. FTY720 might counteract these secondary injuries and thereby prevent their pathological consequences."
"Our data suggest that targeting S1P receptors with FTY720 is an attractive therapeutic approach for SCI," Dr. Sakata concludes. "However, further evaluation utilizing larger animals such as non-human primates will be necessary to confirm its efficacy in treating SCI. Further, strategies targeted at modulating the SIP concentration in injured CNS may lead to new therapeutic approaches towards repairing various CNS disorders."
Source: Eurekalert
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