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Molecular targeted therapy against the blood-brain barrier in multiple sclerosis


Previous therapeutic strategies for multiple sclerosis ( MS ) include the non-selective suppression of systemic immunity ( immunosuppressive agents, such as glucocorticoids, Mitoxantrone and Azathioprine ) and immunomodulation ( type I interferons or intravenous immunoglobulin ).
The recent development of two pivotal drugs, Fingolimod ( Gilenya ) and Natalizumab ( Tysabri ), has resulted in a third category of MS treatment, namely the sequestration of pathogenic T cells.

Natalizumab, a humanized monoclonal antibody that binds to the alpha4-integrin molecule on the surface of circulating lymphocytes and thus blocks very late antigen-4/vascular cell adhesion molecule-1 interactions at the blood-brain barrier ( BBB ), is now widely accepted as a potent tool for treating relapsing–remitting multiple sclerosis.
This drug is epoch-making, as it is the first agent to confirm the efficacy of merely inhibiting the transfer of T cells across the blood-brain barrier in the treatment of multiple sclerosis; however, the risk of a potentially fatal central nervous system opportunistic infection, progressive multifocal leukoencephalopathy, should always be kept in mind.

Because the onset of progressive multifocal leukoencephalopathy might be partly due to the almost total blockage of T cells, including those participating in immune surveillance, the development of novel therapies that selectively inhibit only the entrance of pathogenic T cells is now eagerly awaited.

In addition to the blockade of mononuclear cell intrusion, restoring the integrity of the blood-brain barrier might quickly terminate the process of local inflammation.

In addition, manipulating the blood-brain barrier to enhance the transfer of useful molecules, including a variety of growth factors, could facilitate axonal regeneration.

Therefore, the blood-brain barrier is a promising target of future therapeutic strategies in multiple sclerosis. ( Xagena )

Kanda T, Clin Exp Neuroimmunol 2014; 5, Issue Supplement s1, 28–34

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