Selective Targeting of T and B Cell Populations by Alemtuzumab in the Treatment of Multiple Sclerosis

Abstract

U pstream targeting of both T and B cells is a rational therapeutic approach in multiple sclerosis (MS) in view of how both cell types and the interaction between them contribute to MS pathophysiology. This article will discuss this new way of thinking in MS: the targeting of both T and B cells, with a focus on the recently developed therapy, alemtuzumab (Lemtrada ® , Genzyme, UK). Alemtuzumab depletes T and B lymphocytes, mainly via complement-dependent cytolysis and antibody-dependent cytolysis; depletion of B cells is not an enduring effect compared with the depletion of T cells. After dosing, CD4+ and CD8+ T cells and CD19 B cells decrease initially but increase over the following 11 months. During repopulation after alemtuzumab treatment, there is a shift in the relative proportions of T cell and B cell subsets whereby proportions of regulatory T cells and memory-phenotype T cells are increased and the proportion of naïve T cells is decreased. A switch from a pro-to an anti-inflammatory phenotype and cytokine profile caused by alemtuzumab may underpin the long-lasting suppression of MS activity that has been observed in clinical trials. Alemtuzumab treatment is also associated with a consistently good safety and tolerability profile. Further, alemtuzumab appears to promote neurorehabilitation by improving measures of physical functioning, disability, measures of quality of life, and brain volume loss. Alemtuzumab therefore has the potential to reduce disease burden and improve substantially the prognosis for patients with MS.

Regenerative Medicine in Urogynecology: Where We Are and Where We Want to Be

“…The results are overall promising, although there is significant heterogeneity in the preparation and application of PRP between studies that included a very small number of participants and lacked comparison groups 35 and, therefore, it is currently difficult to assess whether there is true efficacy. The two ongoing randomized controlled trials (NCT05390970 42 and NCT05112718 43 ) evaluating the efficacy of PRP compared to placebo for SUI will provide rigorous data regarding the PRP's efficacy for this PFD.…”