Multiple Sclerosis Therapeutics: Current status and future prospects of Multi Sclerosis therapeutics

Multiple sclerosis (MS) is a chronic inflammatory disease that affects the central nervous system. It is characterized by demyelination and axonal damage of nerve fibers throughout the brain and spinal cord. The exact cause of MS is still unknown, however it is thought to be an autoimmune disorder where the body's own immune system attacks the protective sheath (myelin) that covers nerve fibers. While there is no cure for MS currently, over the past few decades, significant progress has been made in developing disease-modifying therapies that can help manage MS symptoms and reduce the frequency and severity of relapses.

First-line Immunomodulatory Therapies

The first class of FDA-approved therapies for relapsing forms of MS are immunomodulatory drugs. Multiple Sclerosis Therapeutics These work to calm the overactive immune system and reduce inflammation in the central nervous system. Some of the commonly prescribed first-line immunomodulatory drugs include:

Interferon beta-1a and beta-1b: These are some of the first MS drugs approved. They work by stimulating the production of interferon, which helps regulate the immune system. They are administered via intramuscular or subcutaneous injection. Side effects may include flu-like symptoms.

Glatiramer acetate (Copaxone): This comes as a daily subcutaneous injection. It reduces immune cell activity in the brain and spinal cord. Common side effects include injection site reactions.

Teriflunomide (Aubagio): This oral medication works by inhibiting an enzyme called dihydroorotate dehydrogenase, which plays a role in T and B cell activation. Side effects can include diarrhea, nausea, upper respiratory tract infections, and liver function abnormalities.

Dimethyl fumarate (Tecfidera): Taken orally twice a day, it has anti-inflammatory and antioxidant properties. Common side effects include flushing, diarrhea, nausea and abdominal pain.

Sphingosine 1-phosphate receptor modulators

A second class of therapies are sphingosine 1-phosphate (S1P) receptor modulators. They work by preventing lymphocyte egress from lymph nodes, reducing their numbers in the central nervous system.

Fingolimod (Gilenya): The first oral treatment approved for relapsing MS. Taken daily, it binds to S1P receptors preventing lymphocytes from leaving lymph nodes. Can cause bradycardia and macular edema.

Siponimod (Mayzent): A selective S1P1 and S1P5 receptor modulator. Taken once daily with food, it reduces lymphocyte migration into the CNS. Common side effects include hypertension and infections such as herpes.

Ozanimod (Zeposia): Also a selective S1P1 and S1P5 receptor modulator. Taken once daily, it helps control MS disease activity. Risk of increased liver enzymes and has a black box warning for increased risk of serious infections.

Monoclonal Multiple Sclerosis Therapeutics

Monoclonal antibodies are also utilized for treatment of relapsing-remitting MS. These bioengineered molecules target specific components of the immune system:

Natalizumab (Tysabri): Infused every 4 weeks, it prevents immune cells from entering the brain and spinal cord. Indicates significant reduction of MS relapses but there is increased risk of progressive multifocal leukoencephalopathy, a rare viral infection of the brain.

Ocrelizumab (Ocrevus): A humanized monoclonal antibody infused twice yearly that selectively targets and depletes CD20-expressing B cells. This lessens inflammation and slows MS progression. There have been a few cases of meningitis and other serious infections reported.

Cladribine (Mavenclad): Given as two short courses of treatment a year apart. It selectively reduces lymphocyte counts. Effective in reducing relapses in relapsing-remitting MS. There is a high risk of infection including herpes virus infection.

New and Emerging Therapies

Research into new mechanisms of action for treating MS continues at a rapid pace. Some promising new therapeutics in clinical development include:

Ofatumumab: A fully human monoclonal antibody targeting CD20 molecules on B cells. Being studied for efficacy and safety in relapsing forms of MS.

Evobrutinib: An oral Bruton's tyrosine kinase inhibitor in Phase 3 trials that may reduce inflammation by blocking B cell activation.

Siponimod: In addition to being approved, it is undergoing trials in other MS populations including primary progressive MS.

Masitinib: An oral tyrosine kinase inhibitor thought to reduce neuroinflammation and neurodegeneration. Phase 3 trials ongoing in primary progressive MS.

Lesinurad: In Phase 2 testing for progressive MS, it may protect oligodendrocytes and promote myelin repair.

Significant progress has been made over the past few decades in developing therapies that can reduce relapses and disease activity in MS. Current first-line treatments include immunomodulators and S1P receptor modulators, both of which can help control relapses when taken continuously. Monoclonal antibodies provide another option particularly for aggressive forms of relapsing MS. Meanwhile, research into new mechanisms of action holds promise for a potential disease-modifying effect in progressive MS subtypes. Continued development of safe and effective MS therapies that halt disability progression remains an area of high priority.

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