Sphingosine 1-Phosphate Receptor Modulators for Multiple Sclerosis

AbstractFingolimod (Gilenya) received regulatory approval from the US FDA in 2010 as the first-in-class sphingosine 1-phosphate (S1P) receptor (S1PR) modulator and was the first oral disease-modifying therapy (DMT) used for the treatment of the relapsing forms of multiple sclerosis (MS). Development of this new class of therapeutic compounds has continued to be a pharmacological goal of high interest in clinical trials for treatment of various autoimmune disorders, including MS. S1P is a physiologic signaling molecule that acts as a ligand for a group of cell surface receptors. S1PRs are expressed on various body tissues and regulate diverse physiological and pathological cellular responses involved in innate and adaptive immune, cardiovascular, and neurological functions. Subtype 1 of the S1PR (S1PR1) is expressed on the cell surface of lymphocytes, which are well known for their major role in MS pathogenesis and play an important regulatory role in the egress of lymphocytes from lymphoid organs to the lymphatic circulation. Thus, S1PR1-directed pharmacological interventions aim to modulate its role in immune cell trafficking through sequestration of autoreactive lymphocytes in the lymphoid organs to reduce their recirculation and subsequent infiltration into the central nervous system. Indeed, receptor subtype selectivity for S1PR1 is theoretically favored to minimize safety concerns related to interaction with other S1PR subtypes. Improved understanding of fingolimod ’s ...
Source: CNS Drugs - Category: Neurology Source Type: research