This study investigated the effect of B-cell* depletion on central nervous system white and gray matter pathology in experimental autoimmune encephalomyelitis (EAE) in common marmosets, a relevant preclinical model of multiple sclerosis.
B cells are the cell of the immune system that make proteins called antibodies.
EAE was induced in 14 marmosets by immunization with proteins from human myelin. At 21 days after immunization, B-cell depletion was achieved by weekly intravenous injections of a human-anti-human CD20 antibody that cross-reacts with marmoset CD20. MRI showed widespread brain white matter demyelination in control marmosets that was absent in CD20 antibody-treated marmosets. High-contrast postmortem MRI showed white matter lesions in 4 of the 7 antibody-treated marmosets, but these were significantly smaller than those in controls. The same technique revealed gray matter lesions in 5 control marmosets, but none in antibody-treated marmosets. Detailed analysis confirmed that inflammation, demyelination, and axonal damage were substantially reduced in brain, spinal cord, and optic nerves of CD20 antibody-treated marmosets.
Conclusion: B-cell depletion profoundly reduced the development of both white and gray matter lesions in the marmoset CNS. These data underline the central role of B cells in CNS inflammatory-demyelinating disease.
“I am not sure about the ethics of this study as anti-CD20 treatment has already been shown to be effective in MS and is in late stage development in phase 3 in both relapsing-remitting and primary progressive MS. Do you we need to do trials in primates at this stage? What do you think?”
Trials of anti-CD20 in MS: