auy-954 and Guillain-Barre-Syndrome

Experimental autoimmune neuritis (EAN) is a T cell-mediated autoimmune inflammatory demyelinating disease of the peripheral nervous system and an animal model of human inflammatory demyelinating polyradiculoneuropathy. AUY954, which targets selectively the sphingosine-1-phosphate receptor 1 (S1P(1)), is known to sequester lymphocytes into secondary lymphoid tissues. In EAN rats, AUY954 greatly prevented paraparesis if administrated from the day of immunization. T cell, B cell, and macrophage infiltration, inflammatory demyelination, and local expression of interleukine-17 and matrix metalloproteinase-9 in sciatic nerves of EAN rats were significantly decreased by AUY954 treatment. Therefore, S1P(1) modulation might be a potential treatment option for inflammatory neuropathies.

Topics: Animals; B-Lymphocytes; beta-Alanine; Chemotaxis, Leukocyte; Disease Models, Animal; Guillain-Barre Syndrome; Immunologic Factors; Interleukin-17; Macrophages; Male; Matrix Metalloproteinase 9; Neuritis, Autoimmune, Experimental; Paraparesis; Rats; Rats, Inbred Lew; Receptors, Lysosphingolipid; Sciatic Nerve; T-Lymphocytes; Thiophenes; Treatment Outcome