Systemic immunosuppressive treatments:
- 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%.
- 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:
- Fingolimod (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 (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.
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