Immune System Changes May Increase Efficacy of Treatment for Secondary Progressive MS

Shifting towards an anti-inflammatory and suppressive homeostatic immune system may contribute to increased clinical efficacy of siponimod in patients with secondary progressive multiple sclerosis (SPMS), a recent study in JCI Insight reported.

Researchers conducted a multi-centered, randomized, double-blind, placebo controlled, AMS04 mechanistic study, which included 36 patients with SPMS. Participants’ gene expression profiles were assessed using RNA.

“Secondary progressive multiple sclerosis follows an initial course of relapsing-remitting MS (RRMS) and is characterized by chronic disability progression not associated with relapses,” authors said. “MS involves both inflammation and neurodegeneration, and although the underlying mechanisms are not well understood, progressive MS is thought to be driven primarily by neurodegenerative processes.”

The researchers performed flow cytometry-based assays in order to analyze the immune cell composition and microarray gene expression on peripheral blood from siponimod-treated participants with SPMS, according to the authors.

The analysis demonstrated that immune-associated genes involved in T and B cell activation and receptor signaling were significantly decreased by siponimod.

“Analysis done by flow cytometry showed that within the remaining lymphocyte subsets, there was a reduction in the frequencies of CD4 and CD8 naïve T cells and central memory cells, while T effector memory cells, anti-inflammatory Th2, and T regulatory cells were enriched,” authors said. They continued, “Transitional Bregs and B1 cell subsets were enriched, shifting the balance in favor of regulatory B cells over memory B cells.”

In addition, results showed a positive correlation between regulatory T cells and regulatory B cells in participants treated with siponimod.

“Our study shows that siponimod reduces the inflammatory profile in the peripheral blood through enhancement of regulatory cell populations. These effects of siponimod are expected to partially drive its efficacy in SPMS,” authors said.

Reference:

Wu Q, Mills E A, Wang Q, et al. Siponimod enriches regulatory T and B lymphocytes in secondary progressive multiple sclerosis [published online January 14, 2020]. JCI Insight. doi: 10.1172/jci.insight.134251.