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- Pipeline Molecules
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Our mission is to provide healthcare professionals with unbiased clinical research information, easily.
Currently, you can access the following clinical trials being conducted worldwide:
The safety and efficacy of the agents and/or uses under investigation have not been established. There is no guarantee that the agents will receive health authority approval or become commercially available in any country for the uses being investigated
Sphingosine-1-phosphate (S1P) is a lipid signaling molecule that regulates numerous biological processes through its interaction with a family of G protein–coupled receptors (S1P1 to S1P5).1 Preclinical studies have demonstrated the efficacy of S1P receptor–targeting agents in animal models of multiple sclerosis (MS).2 S1P receptors are expressed throughout the body.1,3-7 Those that appear to be important in MS include S1P1 and S1P4 receptors, which are primarily expressed on naive B and T lymphocytes,1,7 and S1P5 receptors, which are expressed on oligodendrocytes and natural killer cells.8-10
In lymphoid tissue, S1P binds to S1P1 on the surface of lymphocytes. Triggered by an S1P gradient, B and T lymphocytes exit lymphoid tissue and enter circulation.2 S1P signaling does not affect subsets of lymphocytes that do not travel through the lymphoid tissue, and thus remain in circulation for immune surveillance against infections and tumors.11 Lymphocytes (including B and T cells) play a critical role in regulating pro-inflammatory and anti-inflammatory activity. In both normal states and in MS, certain types of lymphocytes transit through lymphoid tissue, but engagement of S1P1 leads to their release. Autoreactive naive and central memory T cells, and B cells transit through lymphoid tissue and leave the lymphoid tissue in an S1P1-dependent fashion and infiltrate the blood brain barrier.12-15 In the central nervous system (CNS), autoreactive T and B cells may contribute to chronic inflammatory processes that possibly result in myelin and axonal damage. Taken together, these preclinical data suggest that targeting the S1P pathway to block S1P gradient–dependent migration of lymphocytes may help reduce chronic inflammation that contributes to myelin and axonal damage in MS.2,16-18