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What Are S1P Receptor Modulators?

Posted on July 23, 2021
Medically reviewed by
Evelyn O. Berman, M.D.
Article written by
Brooke Dulka, Ph.D.

  • Sphingosine-1-phosphate (S1P) receptor modulators are a newer class of disease-modifying therapies that can be used to treat relapsing forms of multiple sclerosis (MS).
  • S1P receptor modulators are taken orally once or twice a day.
  • S1P receptor modulators are believed to work by reducing the activity of immune cells in the brain and spinal cord.

Although multiple sclerosis cannot yet be cured, there are medications that can slow its progression and reduce symptoms. In recent years, a newer class of disease-modifying therapy (DMT) known as sphingosine-1-phosphate receptor modulators have been approved to treat relapsing forms of MS.

S1P receptor modulators are drugs that help regulate the immune system. S1P receptor modulators are believed to work by blocking the S1P receptors found on the surface of lymphocytes — a type of white blood cell — that contribute to MS attacks. Generally, S1P receptor modulators are oral medications taken once or twice daily.

How Do S1P Receptor Modulators Work?

Receptors are like the “locks” on cells within the body, and antagonist drugs can function like “keys” to open them. S1P receptor modulators are believed to work via indirect antagonism of the S1P receptor.

An antagonist is a drug that reduces activity at a given receptor site. S1P receptor modulators are indirect antagonists because they don’t work on the receptor site directly, but bind to a different target that influences the S1P receptors’ activity.

The effect of S1P receptor modulators is to trap lymphocytes within the lymph nodes, away from the brain and spinal cord — also called the central nervous system or CNS. If lymphocytes can’t enter the CNS, they can’t contribute to MS attacks. There are several subtypes of S1P receptors, and each of the currently available S1P receptor modulators acts on the receptor subtypes differently. This leads to specific effects from each S1P receptor antagonist drug, making some S1P receptor modulators better options for one type of MS over another type.

What S1P Receptor Modulators Are Currently Available?

There are now several S1P receptor modulators approved to treat MS. These drugs include Gilenya (fingolimod), Mayzent (siponimod), Ponvory (ponesimod), and Zeposia (ozanimod).

S1P Receptor Modulators for Relapsing Forms of MS
Approved To Treat

Gilenya

(fingolimod)

Mayzent

(siponimod)

Ponvory

(ponesimod)

Zeposia

(ozanimod)

Clinically isolated syndrome (CIS) X X X X
Relapsing-remitting MS (RMSS) X X X X
Active secondary progressive MS (SPMS) X X X X
Sources Reference Reference Reference Reference

When Are S1P Receptor Modulators Prescribed?

These drugs are typically used for the treatment of various types of MS, which include clinically isolated syndrome, relapsing-remitting MS, and active secondary progressive MS. These forms of MS may be characterized by attacks (or relapses) of new or increasing neurological symptoms. CIS can progress to RRMS, and RRMS can likewise progress to SPMS. Unless treated with DMTs, MS progression can lead to increases in disability and reduced quality of life.

Learn more about relapsing forms of MS.

According to the Consortium of Multiple Sclerosis Centers, any approved drug for MS can be prescribed as a first-line treatment for relapsing forms of MS. However, S1P receptor modulators are more likely to be prescribed for relapsing MS that seems to be progressing. This is because of the S1P receptor modulators’ mechanism of action. Specifically, by preventing lymphocytes from entering the central nervous system, MS progression can be slowed. This has been scientifically shown in phase 3 clinical trials of S1P drugs such as Mayzent, where a significant reduction in disability progression was observed compared to placebo.

Remember, although there is no cure for MS, DMTs are proven to slow MS disease progression. People with MS can live with an improved quality of life with DMTs, including S1P receptor modulators.

Read more about what to expect when starting an S1P receptor modulator.

Talk With Others Who Understand

MyMSTeam is the social network for people with multiple sclerosis and their loved ones. On MyMSTeam, more than 170,000 members come together to ask questions, give advice, and share their stories with others who understand life with multiple sclerosis.

Are you living with multiple sclerosis? Have you taken an S1P receptor modulator for your MS? Share your experience in the comments below, or start a conversation by posting on your Activities page.

Evelyn O. Berman, M.D. is a neurology and pediatric specialist and treats disorders of the brain in children. Review provided by VeriMed Healthcare Network. Learn more about her here.
Brooke Dulka, Ph.D. is a freelance science writer and editor. She received her doctoral training in biological psychology at the University of Tennessee. Learn more about her here.

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