Delving into the Latest Updates on S1P (York Pharma) with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Sphingosine-1-phosphate (Berlin Free University), Sphingosine-1-phosphate (York Pharma)

+ [1]

Target

S1PR1

Mechanism

S1PR1 agonists(Sphingosine 1-phosphate receptor Edg-1 agonists)

Therapeutic Areas

Skin and Musculoskeletal Diseases

Active Indication-

Inactive Indication

Skin Diseases

Originator Organization

Freie Universität Berlin

Active Organization-

Inactive Organization

York Pharma Plc

Freie Universität Berlin

Drug Highest PhaseDiscontinuedDiscovery

First Approval Date-

Regulation-

BACKGROUNDSjögren' s syndrome (SS) is a chronic autoimmune disease that causes multiple lesions. Regulatory T (Treg) cells play an important role in the maintenance of immune homeostasis. Weakened Treg-cell-mediated immunosuppression may aggravate SS symptoms by inducing lymphocyte infiltration into the salivary glands. Although Treg cell egress from such glands requires sphingosine-1-phosphate (S1P), the specific effects of S1P on SS-like symptoms remain unclear.AIMSTo examine the effect of S1P on SS-like symptoms and the crosstalk between such symptoms and autophagy in non-obese diabetic (NOD) mice.METHODSNOD mice were taken as SS model mice. Balb/c mice served as controls. Serum anti-SSA and anti-SSB antibodies were quantitated via ELISA. Submandibular gland tissues were subjected to haematoxylin-and-eosin staining, and extracts thereof to reverse transcription-polymerase chain reaction. The numbers of Treg cells; and the levels of cytokines, LC3, and SPHK1 were measured via flow cytometry (FCM). The Treg immunosuppression capacity was assessed in co-culture experiments.RESULTCompared to untreated NOD mice, mice treated with S1P exhibited milder disease, and higher numbers of functional Treg cells. FCM revealed that S1P restored LC3 expression in Treg cells, but had little effect on the LC3 levels of Teff cells. RT-PCR showed that S1P increased the expression levels of mRNAs encoding Foxp-3, SPHK1, S1PR1, and LC3 in submandibular glands (SMGs). After administration of PF-543, the disease became aggravated; lymphocyte infiltration into SMGs increased and LC3 expression fell.CONCLUSIONS1P therapy alleviated SS-like symptoms in NOD mice by increasing the number of Treg cells, by restoring Treg cell function, and by positively regulating autophagy via crosstalk. Such therapy may be a new and valuable SS treatment option.

01 Dec 2024·Immunology Letters

Fingolimod, an antagonist of sphingosine 1-phosphate, ameliorates Sjögren's syndrome by reducing the number of STAT3–induced germinal center B cells and increasing the number of Breg cells

Article

Author: Cho, Mi-La ; Jhun, JooYeon ; Lee, Yeon Su ; Yang, Seung Cheon ; Hwang, Sun-Hee ; Woo, Jin Seok ; Lee, Kun Hee ; Lee, A Ram ; Choi, Jeong Won

BACKGROUNDSjögren's syndrome (SS) is an autoimmune disease caused by infiltrating lymphocytes. FTY720 affects the S1P signaling pathway, which plays a role in T and B cell migration from secondary lymphoid tissues to target organs. In this study, we investigate the regulatory mechanism of FTY720 in the context of SS.METHODFTY720 was given orally every day to NOD mice. The salivary flow rate (SFR) and blood glucose level were assayed every 3 weeks. Histopathological features were investigated at the end of the study. In vitro, FTY720 was added to mouse splenocytes, and changes in the lymphocyte subsets were assessed.RESULTSIn vivo, FTY720 increased the SFR and reduced the blood glucose level. The salivary gland histological score and infiltration of the salivary glands by B and T cells were dramatically decreased. Furthermore, STAT expression in the salivary gland was decreased. In vitro, FTY720 inhibited Th17 cells, while increasing regulatory T (Treg) cells, respectively. Also, FTY720 decreased and increased the numbers of germinal center (GC) B cells and regulatory B cells (Breg cells), respectively. FTY720 decreased the IgG level in culture supernatants. Also, STAT3 activation was decreased by FTY720.CONCLUSIONOur results show the therapeutic potential of FTY720 in the context of SS; FTY720 prevents lymphocyte migration from secondary lymphoid organs to target organs.

01 Nov 2024·CNS Drugs

Ozanimod: A Review in Relapsing Forms of Multiple Sclerosis

Review

Author: Nie, Tina ; Syed, Yahiya Y ; Syed, Yahiya Y.

Ozanimod (Zeposia^®), an orally administered sphingosine 1-phosphate (S1P) receptor modulator (S1PRM) that is selective for the S1P₁ and S1P₅ receptor subtypes, is approved in the USA for relapsing forms of multiple sclerosis (RMS). In pivotal phase III clinical trials in patients with RMS, ozanimod significantly reduced annualised relapse rates and the number of new or enlarging T2 lesions and gadolinium-enhancing lesions, and was associated with reduced brain volume loss, compared with interferon (IFN)-β1a. However, there were no significant differences in 3- and 6-month disability progression between the groups. Ozanimod was generally well tolerated, with the most common adverse reactions including upper respiratory tract infection and hepatic transaminase elevation. Efficacy and tolerability were sustained over more than 6 years with continued treatment. S1PRM-related adverse events seen with ozanimod are generally manageable with screening and/or monitoring. Notably, ozanimod does not require first-dose cardiac monitoring in the USA. In conclusion, ozanimod is a valuable once-daily oral disease-modifying therapy that extends the available treatment options for patients with RMS.

100 Deals associated with S1P (York Pharma)

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