Alemtuzumab (Lemtrada), a multiple sclerosis (MS) therapy, prevented the formation of B-cell aggregates and disrupted existing ones in a mouse model of the disease, according to a new study published in the Journal of Neuroinflammation. When administered at the peak of disease, the drug also lowered disease activity.

According to the study, recent reports of treatment failure in individual patients with subsequent severe and possible B cell-mediated relapses underscored a need for further research.

Although immune pathology of MS has traditionally been considered to be mainly T cell-driven, more recent experimental data suggest an interaction between T cells and B cells. Given the ongoing controversy about B-cell involvement in the brains of patients with progressive MS, the researchers sought to provide a better understanding of the treatment’s effects on the B-cell component of the disease.

For the study, they used myelin basic protein-proteolipid protein-induced experimental autoimmune encephalomyelitis (EAE) in mice as a B cell-dependent model of MS. Mice were treated with either alemtuzumab or a control antibody at peak of EAE or at 60 days after onset for 5 consecutive days. Disease was monitored for 10 days, according to the study.

The researchers found that treatment with alemtuzumab attenuated EAE only when administered at peak of disease; however, the treatment almost completely depleted B-cell infiltration of the CNS and B-cell aggregates. Additionally, treated mice showed less nerve cell damage in the spinal cord and cerebellum.

“Interestingly, treatment not only prevented the formation of aggregates, but also disrupted already existing aggregates in MP4-induced EAE,” the researchers wrote in the study. “The clinical relevance of B cell aggregates in the brain of MS patients is still subject to debate, but an association with an earlier disease onset, progression, and death and with more severe cortical pathology is assumed.”

Further studies will be needed to determine whether alemtuzumab is equally effective in depleting B-cell aggregates in humans with MS and whether it is associated with clinical benefit, the study concluded.

“In order to prevent further or even reverse pre-existing neurological disabilities, the search for new treatment options for MS patients focuses not only on immune modulation, but also on neuroprotection,” the researchers wrote.

Reference

Simon M, Ipek R, Homola GA, et al. Anti-CD52 antibody treatment depletes B cell aggregates in the central nervous system in a mouse model of multiple sclerosis. Journal of Neuroinflammation. 2018. https://doi.org/10.1186/s12974-018-1263-9