Effects of Ocrelizumab on B-cell Tolerance Defect in Relapsing Multiple Sclerosis
Status:
Active, not recruiting
Trial end date:
2024-03-01
Target enrollment:
Participant gender:
Summary
B-cells have an important role in the pathogenesis of multiple sclerosis (MS). Ocrelizumab, a
medication that targets B-cells have been found to be highly effective in stopping the
disease activity in relapsing-remitting MS.
The efficacy of ocrelizumab might be related to the specific pattern of B-cell tolerance
defect in patients with MS and the potential of its normalization with treatment with
ocrelizumab. By analyzing the reactivity of recombinant antibodies expressed from single
B-cells, the investigators' collaborators have demonstrated that the pattern of B-cell
tolerance defect is different in people with MS who only display an impaired removal of
developing autoreactive B-cells in the periphery while central B-cell tolerance in the bone
marrow is functional in most patients. In contrast, patients with rheumatoid arthritis (RA),
type-1 diabetes (T1D) or Sjögren's syndrome (SS) show defective central and peripheral B-cell
tolerance checkpoints. As a consequence, while anti-B-cell therapy does not correct defective
early B-cell tolerance checkpoints in T1D and only temporarily slows down autoimmune
processes before newly generated autoreactive B-cells likely induce patient relapse, the
investigators postulate that the efficacy of ocrelizumab in MS may be linked to normal
central B-cell tolerance and the production of a normal B-cell and T-cell compartment after
ocrelizumab therapy.
In an open-label study, 10 patients with relapsing MS will be treated with two courses of
ocrelizumab and will be followed clinically and radiologically for at least two and a half
years. Assessment of T and B-cell phenotypes and function at baseline and 18-24 months
post-B-cell depletion will be the primary outcome of the study.