Category Archives: Multiple Sclerosis QA

Q&A: How does Avonex/Rebif/Betaseron treat Multiple Sclerosis?

Avonex_01IFN-b 1a (Avonex, Re-bif); IFNb 1b (Betaferon)

  • Functions: IFN-b reduces antigen presentation and thereby alters the proliferation of T cells. T cells, when activated and have the right capacity, can destroy myelin proteins that are essential for proper signal transduction. It also reduces the expression of metalloproteinase that is required for T cells to cross the blood brain barrier, thus reducing the number of T cells in the brain and indirectly alleviating the demyelination process.
  • Betaferon: first drug to treat relapsing-remitting MS. It reduces relapse rate by 30%.

For full list of immune-modulating treatments available for MS, click here

Q&A: What are the systemic immunosuppressive treatment of multiple sclerosis (MS)?

Systemic immunosuppressive treatments:

  • Mitoxantrone
    • Functions: It is a topoisomerase II inhibitor that interferes with DNA repair. It can also bind to DNA, so DNA and RNA replication is inhibition. It is found to suppress the proliferation of lymphocytes. And it can also inhibit the migration of macrophage into the central nervous system to suppress more inflammation.
    • Mitoxantrone: the only cytotoxic drug approved to treat relapsing remitting MS, progressive MS, progressive relapsing MS. Treatment for 2 years led to reduction of relapse rate by 64%.

     

  • Cladribine
    • Functions: purine nucleoside that impairs synthesis and repair of DNA.
    • Cladribine: reduce relapse rate; but has side effects: neutropenia, thomboctopenia, panctopenia and increased infection rate. Clinical trials are halted.

Other drugs with specific targets in MS:

  • gilenya2Fingolimod (FTY720)/Gilenya
    • Functions: regulates migration of activated immune cells by activating S1P G-protein coupled receptors, leading to increased sequestering of lymphocytes influx into the lymph node.
    • FTY720: approved for treating for relapse remitting MS; phase II clinical trial showed suppression of relapse.
  • natalizumab-15900_1Natalizumab (anti-a4b1 antibody)
    • Functions: blocking the a4b1 integrin expressed on activated lymphocytes, which a4b1 integrin is required to interact with VCAM-1 on endothelial cells for the activated cells to cross vasculature to the CNS.
  • Alemtuzumab (anti-CD52 antibody)
    • Functions: blocking CD-52 expressed on immune cells. Thus, it will deplete immune cells from circulation.
  • Anti-CD20 (Rituximab, Ocrelizumab)
    • Functions: blocking the CD-20 expressed on B cell, thus it will stop maturation of B cell into antibody secreting plasma cells.

Related: Immune modulating agents for treating MS


Reference:Current Treatment Strategies for Multiple Sclerosis – Efficacy Versus Neurological
Adverse Effects. Martin S. Weber, Til Menge, Klaus Lehmann-Horn, Helena C. Kronsbein, Uwe Zettl, Johann Sellner,
Bernhard Hemmer1 and Olaf Stüve

Q&A: What are the current treatments for multiple sclerosis (MS)?

  • Immune modulating agents:

    • Avonex_01IFN-b 1a (Avonex, Re-bif); IFNb 1b (Betaferon)
      • Functions: IFN-b reduces antigen presentation and thereby alters the proliferation of T cells. T cells, when activated and have the right capacity, can destroy myelin proteins that are essential for proper signal transduction. It also reduces the expression of metalloproteinase that is required for T cells to cross the blood brain barrier, thus reducing the number of T cells in the brain and indirectly alleviating the demyelination process.
      • Betaferon: first drug to treat relapsing-remitting MS. It reduces relapse rate by 30%.

       

    • Copaxone2Glatiramer acetate (Copazone)
      • Functions: GA is a mixture of synthetic peptides to mimic a major component of the myelin protein. The mechanism of GA is unclear: it has been shown to differentiate naive T cells into Th2, increase regulatory T cells (that can inhibit proinflammatory T cells), modulate CD8 cytotoxic T cells, modulate B cells.
      • Copazone: demonstrated reduction of relapse rate of 30%

       

    • Laquinimod
      • Functions: modulate cytokine secretion from peripheral blood lymphocytes; weaken pro-inflammation, impair cell traffick into the CNS
      • Laquinimod: can be administered orally. 0.6mg per day is shown to decrease the number of lesions by 40%. Currently Phase III trial is finished: company said the clinical trial has failed, but it is shown to reduce relapse rate and progression.

Related Article: Systematically immunosupressive treatments for MS


Reference:Current Treatment Strategies for Multiple Sclerosis – Efficacy Versus Neurological
Adverse Effects. Martin S. Weber, Til Menge, Klaus Lehmann-Horn, Helena C. Kronsbein, Uwe Zettl, Johann Sellner,
Bernhard Hemmer1 and Olaf Stüve