Rinsho Shinkeigaku (Clinical Neurology)

The 46th Annual Meeting of the Japanese Society of Neurology

Synthetic glycolipid ligands as novel therapeutics for multiple sclerosis

Takashi Yamamura, M.D., Ph.D.

Department of Immunology, National Institute of Neuroscience, NCNP

Our previous works indicate that regulatory cells such as natural killer (NK) cells and NKT cells could play an active role in maintaining the remission state of MS. We have therefore adopted a strategy for developing the future MS therapy by targeting NKT cells. The unique glycolipid-reactive lymphocytes are known to produce a large quantity of Th2 cytokines such as IL-4 when encountering their ligands like α-galactosylceramide (α-GC). Whereas most of the NKT ligands so far described would stimulate both Th1 and Th2 cytokine production by NKT cells, the synthetic compound OCH, an analogue of α-GC with a shorter lipid tail, is the one which selectively induces IL-4 production. Given this property, oral or intraperitoneal OCH administration would prohibit the development of a variety of Th1-meediated pathology, including EAE, collagen-induced arthritis, type 1 diabetes, DSS-induced colitis and acute GVHD by inducing Th2 bias. This review paper summarizes the recent publications and our unpublished results related to the efficacy of OCH and to the molecular mechanism accounting for the Th2 inducing property of OCH.

(CLINICA NEUROL, 45: 909|911, 2005)
key words: multiple sclerosis, autoimmune disease, NKT cells, immunotherapy, IL-4

(Received: 26-May-05)