Accumulated evidence has shown the protective effects of S1P receptor modulators on MS and its animal model, experimental autoimmune encephalomyelitis (EAE).
Siponimod was recently approved by United States Federal Drug Administration for relapsing MS and active secondary progressive MS. Other S1P receptor modulators are being studied in phase 3 trials for relapsing MS. Cladribine received FDA approval as treatment for relapsing and active secondary progressive MS. Autologous hematopoetic stem-cell transplantation may be an option for treatment-refractory MS.
FTY720 is a sphingosine 1 phosphate (S1P) receptor agonist approved for the treatment of multiple sclerosis, which is a chronic inflammatory autoimmune disorder.
FTY720 (Fingolimod) is a known sphingosine-1-phosphate (S1P) receptor agonist that exerts strong anti-inflammatory effects and was approved as the first oral drug for the treatment of multiple sclerosis by the US food and drug administration (FDA) in 2010.
Additionally, the neuroprotective potential of an S1P receptors (S1PR) modulator, fingolimod (FTY720), in multiple sclerosis (MS) and numerous other diseases has been observed over the past decade.
Fingolimod hydrochloride (FTY720) is a first-in-class of sphingosine-1-phosphate (S1P) receptor modulator approved to treat multiple sclerosis by its phosphorylated form (FTY720-P).
Our data may be valuable for comparing the effects of novel S1P receptor modulating agents, which may be a therapeutic option for patients with secondary progressive MS as well.
Here we set out to determine whether FTY720, a molecule that binds sphingosine-1-phosphate (S1P) receptors and with known immunosuppressant effects mediating its therapeutic action in multiple sclerosis (MS), might modulate the impact of infection in a mouse model of AD.
Targeting S1P receptors for inflammatory conditions has been successful in clinical trials leading to approval of the non-selective S1P modulator, fingolimod, for relapsing forms of multiple sclerosis.
Fingolimod, is a recognized modulator of S1P receptors, and is the first orally active disease-modifying therapy that has been approved for the treatment of multiple sclerosis.
Compared to fingolimod (ie, precursor of the S1P modulators commercially available for the treatment of relapsing-remitting [RR] multiple sclerosis [MS]), siponimod exhibits selective affinity for types 1 and 5 S1P receptor, leading to a lower risk of adverse events that are mainly induced by S1P3 receptor activation, such as bradycardia and vasoconstriction.
In this article, we will review how S1P receptor may be a promising therapeutic target for SP-MS and other autoimmune diseases such as psoriasis, polymyositis and lupus.
Here, we show involvement of Cd38, Cxcr4 and Akt and confirm these findings by the use of Cd38-knockout (B6.129P2-Cd38<sup>tm1Lnd</sup>/J) mice, S1P-receptor modulation during EAE and quantitative expression analysis in individuals with MS.
Thus S1P receptor signaling regulates human B-cell circulation and might be a factor contributing to the pathology of MS, chronic lymphocytic leukemia, and primary immunodeficiencies.
Fingolimod-an S1PR modulator approved for the treatment of relapsing MS in some countries-is thought to act by downmodulating lymphatic S1P subtype 1 receptors.
Our data demonstrate that reactive astrocytes in MS lesions and cultured under proinflammatory conditions strongly enhance expression of S1P receptors 1 and 3.
FTY720 (fingolimod) is a first-in-class sphingosine 1-phosphate (S1P) receptor modulator that was highly effective in Phase II clinical trials for Multiple Sclerosis (MS).
This review provides an overview on S1P activities and S1P receptor function in health and disease, and summarizes the clinical experience with FTY720 in transplantation and multiple sclerosis.