siponimod has been researched along with ponesimod* in 3 studies
3 review(s) available for siponimod and ponesimod
Article | Year |
---|---|
Sphingosine 1-phosphate receptor modulators in multiple sclerosis and other conditions.
The sphingosine 1-phosphate (S1P) signalling pathways have important and diverse functions. S1P receptors (S1PRs) have been proposed as a therapeutic target for various diseases due to their involvement in regulation of lymphocyte trafficking, brain and cardiac function, vascular permeability, and vascular and bronchial tone. S1PR modulators were first developed to prevent rejection by the immune system following renal transplantation, but the only currently approved indication is multiple sclerosis. The primary mechanism of action of S1PR modulators in multiple sclerosis is through binding S1PR subtype 1 on lymphocytes resulting in internalisation of the receptor and loss of responsiveness to the S1P gradient that drives lymphocyte egress from lymph nodes. The reduction in circulating lymphocytes presumably limits inflammatory cell migration into the CNS. Four S1PR modulators (fingolimod, siponimod, ozanimod, and ponesimod) have regulatory approval for multiple sclerosis. Preclinical evidence and ongoing and completed clinical trials support development of S1PR modulators for other therapeutic indications. Topics: Animals; Azetidines; Benzyl Compounds; Clinical Trials as Topic; Fingolimod Hydrochloride; Humans; Immune System Diseases; Indans; Multiple Sclerosis; Nervous System Diseases; Oxadiazoles; Signal Transduction; Sphingosine 1 Phosphate Receptor Modulators; Sphingosine-1-Phosphate Receptors; Thiazoles | 2021 |
Multiple sclerosis.
Multiple sclerosis (MS) is the most common chronic inflammatory, demyelinating and neurodegenerative disease of the central nervous system in young adults. This disorder is a heterogeneous, multifactorial, immune-mediated disease that is influenced by both genetic and environmental factors. In most patients, reversible episodes of neurological dysfunction lasting several days or weeks characterize the initial stages of the disease (that is, clinically isolated syndrome and relapsing-remitting MS). Over time, irreversible clinical and cognitive deficits develop. A minority of patients have a progressive disease course from the onset. The pathological hallmark of MS is the formation of demyelinating lesions in the brain and spinal cord, which can be associated with neuro-axonal damage. Focal lesions are thought to be caused by the infiltration of immune cells, including T cells, B cells and myeloid cells, into the central nervous system parenchyma, with associated injury. MS is associated with a substantial burden on society owing to the high cost of the available treatments and poorer employment prospects and job retention for patients and their caregivers. Topics: Azetidines; Benzyl Compounds; Demyelinating Diseases; Humans; Indans; Magnetic Resonance Imaging; Multiple Sclerosis; Oxadiazoles; Risk Factors; Thiazoles; Tomography, X-Ray Computed | 2018 |
Sphingosine 1-Phosphate Receptor Modulators for the Treatment of Multiple Sclerosis.
Sphingosine 1-phosphate receptor (S1PR) modulators possess a unique mechanism of action in the treatment of multiple sclerosis (MS). Subtype 1 of the S1PR is expressed on the surface of lymphocytes and is important in regulating egression from lymph nodes. The S1PR modulators indirectly antagonize the receptor's function leading to sequestration of lymphocytes in the lymph nodes. Fingolimod was the first S1PR modulator to receive regulatory approval for relapsing-remitting MS after 2 phase III trials demonstrated potent efficacy, safety, and tolerability. Fingolimod can cause undesirable effects as a result of its interaction with other S1PR subtypes, which are expressed in diverse tissues, including cardiac myocytes. As such, agents that more selectively target subtype 1 of the S1PR are of interest and are at various stages of development. These include ponesimod (ACT128800), siponimod (BAF312), ozanimod (RPC1063), ceralifimod (ONO-4641), GSK2018682, and MT-1303. Data from phase II trials and early results from phase III studies have been promising and will be presented in this review. Of special interest are results from the EXPAND study of siponimod, which suggest a potential role for S1PR modulators in secondary progressive MS. Topics: Animals; Azetidines; Benzyl Compounds; Clinical Trials as Topic; Fingolimod Hydrochloride; Humans; Immunologic Factors; Indans; Indoles; Multiple Sclerosis; Naphthalenes; Oxadiazoles; Propanolamines; Receptors, Lysosphingolipid; Thiazoles; Treatment Outcome | 2017 |