Anti-CD20 Disrupts Meningeal B-Cell Aggregates in a Model of Secondary Progressive Multiple Sclerosis.Roodselaar J, Zhou Y, Leppert D, Hauser AE, Urich E, Anthony DC.Neurol Neuroimmunol Neuroinflamm. 2021 Mar 2;8(3):e975.
Objective: Therapies targeting B cells have been used in the clinic for multiple sclerosis (MS). In patients with relapsing MS, anti-CD20 therapy often suppresses relapse activity; yet, their effect on disease progression has been disappointing. Most anti-CD20 therapeutic antibodies are type I (rituxumab and ocrelizumab), but within the unique microenvironment of the brain, type II antibodies (one that kills B cells directly) may be more beneficial, as type II antibodies exhibit reduced complement-dependent cytotoxicity and they have an increased capacity to induce direct cell death that is independent of the host immune response.
Methods: We compared the effect of type I with type II anti-CD20 therapy in a new rodent model of secondary progressive MS (SPMS), which recapitulates the principal histopathologic features of MS including meningeal B-cell aggregates. (This was done in adult humanized (hu)CD20 C57BL/6 mice, expressing human CD20 exclusively on B cells).
Focal MS-like lesions were induced by injecting heat-killed Mycobacterium tuberculosis into the cortex (outside of the brain) of MOG-immunized mice. Groups of mice were treated with anti-CD20 antibodies (type I [rituxumab, 10 mg/kg] or type II [GA101, 10 mg/kg]) 4 weeks after lesion initiation, and outcomes were evaluated by immunohistochemistry.
Results: Anti-CD20 therapy decreased the extent of glial activation, significantly decreased the number of B and T lymphocytes in the lesion, and resulted in disruption of the meningeal aggregates. Moreover, at the given dose, the type II anti-CD20 therapy was more efficacious than the type I and also protected against neuronal death.
Conclusions: These results indicate that anti-CD20 may be an effective therapy for SPMS with B-cell aggregates and that the elimination of CD20+ B cells alone is sufficient to cause disruption of aggregates in the brain.
So its amazing and we all made out of star dust..This seems to under pin the use of ocrelizumab in progressive MS, but says Obinutuzumab could be better. So the question now is whether there is enough antibody to do this in MS