The S1P transporter is essential for the development of multiple sclerosis treatment

Multiple sclerosis (MS) is an autoimmune disease
that affects the brain and spinal cord.
In multiple sclerosis, activated immune cells attack the protective layer of myelin around nerve cells, blocking the transmission
of nerve impulses along nerve cells.
Over time, nerves can become permanently damaged or deteriorate
.
Current treatments include monoclonal antibodies and oral sphingosine 1-phosphate (S1P) receptor modulators such as fingolimod and ozanimod
.
However, because S1P receptors are prevalently expressed in many cell types, including vascular cells, S1P receptor modulators have been found to have multiple side effects, such as slowing heart rate and reducing lung function
.
Therefore, more targeted treatments will improve the safety of
S1P drugs.

In a new study led by Nguyen Nam Long, assistant professor at the National University of Singapore's School of Medicine, researchers have shown that targeting the S1P transporter may be effective in treating MS while preserving the cardiovascular function
of S1P signaling.
Previously, Assistant Professor Nguyen Nam Long's team demonstrated in a recent Cell Reports paper that plasma S1P is essential
for vascular maturation and maintaining vascular health.
Building on his previous research, a team led by Assistant Professor Nguyen investigated the reduction of S1P transport
from blood vessels and lymphatic systems through the protein Spns2.

Their findings suggest that eliminating Spns2 after birth leads to a decrease in S1P levels in the lymphatic system, not the circulatory system
.
In addition, they found that different forms of S1P are released into the lymph to attract immune cells to migrate
from the lymph nodes.
Thus, the elimination of Spns2 leads to a decrease
in the level of leukocytes in the blood.
When Spns2-deficient animals were exposed to a disease model of multiple sclerosis, these animals became resistant to the development of multiple sclerosis, while normal animals did not
.
They found that when Spns2 function was blocked, there were fewer
pathogenic white blood cell types in the central nervous system.

Nguyen Nam Long, Assistant Professor of the Department of Translational Research in Immunology (ITRP) and Biochemistry at the National University of Singapore's School of Medicine, explains: "Membrane transporters have been neglected to explore
as drug targets.
This study will propose Spns2, an S1P transporter, as a novel drug target for the treatment of multiple sclerosis and other possible inflammatory diseases to reduce the risk
of multiple side effects from reported S1P receptor modulators.
Dr Nguyen added: "Our team and other researchers around the world are looking for inhibitors of this protein in hopes of discovering a range of new therapies
to fight multiple sclerosis and other inflammations.
"

Associate Professor Veronique Angeli, Director of ITRP, added: "This study by Assistant Professor Nguyen and our researchers at ITRP deepens our understanding of
inflammation in various disease pathologies.
With each new insight, these discoveries can be translated from experimental to clinical, providing people with new treatments to enhance future health
.
”