Depleting B cells in the CNS

Studer V, Rossi S, Motta C, Buttari F, Centonze D. Peripheral B cell depletion and central proinflammatory cytokine reduction following repeated intrathecal administration of rituximab in progressive Multiple Sclerosis. J Neuroimmunol. 2014 Aug 19. pii: S0165-5728(14)00850-9. doi: 10.1016/j.jneuroim.2014.08.617. [Epub ahead of print

B cells and/or the enhanced inflammatory milieu in the subarachnoid space are supposed to have a role in cortical pathology of progressive multiple sclerosis (PMS). The efficacy of intravenous rituximab to deplete circulating B cells is remarkable in MS, and its intrathecal delivery could target compartmentalized inflammation in PMS. We describe the central and peripheral effects of repeated intrathecal rituximab administrations in a patient with severe PMS. Peripheral CD20+ B cells were reduced, while oligoclonal bands were unaffected. Several central proinflammatory cytokines, and markers of neurodegeneration were markedly reduced. 

The agents that affect relapsing MS all can target B cells within the peripheral (Blood) compartment. But many of these agents will not penetrate into the CNS. Some people think that progressive MS may be a problem within the central (CNS) compartment (area). So one way to look at this is to deliver B cell depleting agents into the CNS. This can be come by intrathecal delivery. In this study antibody was delivered in to the central compartment and enough got into the blood to deplete the peripheral compartment. Anti-CD20 depletes many B cells but not the B cells producing antibody (plasma cells) and so maybe you would not think that oligoclonal bands (antibodies within spinal fluid) would be depleted. But some markers of inflammation were reduced.

However is spinal deliver of antibodies a viable treatment? Well if it works one can make a case however it says why not get a drug that can deplete B cells in the peripheral and central compartments. There are already drugs that could do this, why not give them a go...Oh they are outside their patent life so pharma won't development them. 

This is also probably the fate for rituximab.Should neuros do trials with drugs that they may not be able to get pharma to develop?

This is a debate that needs to be debated and solutions found

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