Bonnan M. Intrathecal IgG synthesis: a resistant and valuable target for future multiple sclerosis treatments. Mult Scler Int. 2015;2015:296184. doi: 10.1155/2015/296184
Intrathecal IgG synthesis is a key biological feature of multiple sclerosis (MS). When acquired early, it persists over time. A growing body of evidence suggests that intrathecal Ig-secreting cells may be pathogenic either by a direct action of toxic IgG or by locally secreting bystander toxic products. Intrathecal IgG synthesis depends on the presence of CNS lymphoid organs, which are strongly linked at anatomical level to cortical subpial lesions and at clinical level to the impairment slope in progressive MS. As a consequence, targeting CNS lymphoid lesions could be a valuable new target in MS, especially during the progressive phase. As intrathecal IgGs are end-products of these lymphoid lesions, intrathecal IgG synthesis may be considered as a specific marker of the persistence of these inflammatory lesions. Here we review the effect upon intrathecal IgG synthesis of all drugs ever used in MS. Except for steroids, all these therapeutic strategies, including rituximab, failed to decrease intrathecal IgG synthesis, with the exception of a questionable incomplete action of natalizumab. Thus, IgG synthesis is a robust marker of persistent intrathecal inflammation and its complete normalization should be one of the goals in future therapeutic strategies.
This is a review that states that essentially all treatments, except natalizumab, fail to control antibody production within the central nervous system. Is this the central problem for progressive MS,that the anti-inflammatories fail to get in the brain and so can't stop progression.
Therefore, natalizumab could stop progression if it were that simple. Has this worked in the ASCEND trial of nataliziumab in secondary progressive MS. This should have finished in 2015. However, this study looks like it is being extended but now according to clinical trials.gov the completion date is 2017. Is this being extended because it is working? Why would extend something that is not working?
Or will this address the thought of ProfG that there is a therapeutic lag?
However the effectiveness at blocking depends on how you read the papers there may be others that affect OCB.
Labels: Natalizumab, oligoclonal bands, Tysabri