sphingosine-1-phosphate and Multiple-Sclerosis--Chronic-Progressive

Multiple sclerosis (MS) is a prototype autoimmune disease of the central nervous system (CNS). Currently, there is no drug that provides a cure for MS. To date, all immunotherapeutic drugs target relapsing remitting MS (RR-MS); it remains a daunting medical challenge in MS to develop therapy for secondary progressive MS (SP-MS). Since the approval of the non-selective sphingosine-1-phosphate (S1P) receptor modulator FTY720 (fingolimod [Gilenya®]) for RR-MS in 2010, there have been many emerging studies with various selective S1P receptor modulators in other autoimmune conditions. 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.

Topics: Animals; Autoimmune Diseases; Central Nervous System; Humans; Lysophospholipids; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Receptors, Lysosphingolipid; Sphingosine

Multiple sclerosis is an autoimmune disorder characterized by recurrent attacks against the central nervous system. After many years, certain patients enter a progressive disease phase, characterized by steady clinical deterioration. However, in 10-15% of patients, the disease is progressive from the beginning, and thus diagnosed as Primary Progressive Multiple Sclerosis. Unlike relapsing-remitting forms, progressive MS lacks effective therapy. Astrocytes are a major component of glial cells and are now thought to play a role in disease progression. Sphingosine 1-phophate is a molecule with extensive receptor expression on both immune and glial cells and is also a target of fingolimod, a drug used in relapsing remitting patients that sequesters lymphocytes within lymph nodes. However, because sphingosine 1-phosphate receptors are also expressed in astrocytes, and also because modification of this pathway has shown interesting benefits in animal models of Multiple Sclerosis, this astrocyte pathway has become an interesting target for developing potential new therapeutic approaches for Multiple Sclerosis.

Topics: Astrocytes; Brain; Humans; Lysophospholipids; Multiple Sclerosis, Chronic Progressive; Signal Transduction; Sphingosine