New Findings on How Glatiramer Acetate Works for Multiple Sclerosis

Patients with the relapsing-remitting form of multiple sclerosis have shown improvement with glatiramer acetate. Although it is unclear exactly how the drug works, recently published research has shed light on the ways in which glatiramer acetate affects B cells.

Patients with the relapsing-remitting (RRMS) form of multiple sclerosis (MS) have shown improvement with glatiramer acetate (Copaxone/Teva). But researchers are still uncertain exactly how the drug works.

In research published online Sept. 29 in Jama Neurology a University of Texas Southwestern Medical Center team in Dallas, TX, reported on the ways in which glatiramer acetate affects B cells in these patients.

Nancy Monson, PhD, and colleagues looked at cell samples from 22 patients with MS who were receiving treatment with glatiramer acetate, 22 RRMS patients who were treatment naïve, and 15 healthy controls. They found that glatiramer acetate therapy affects several aspects of dysregulated B-cell function in MS. These changes “may contribute to the therapeutic mechanisms of glatiramer acetate,” the team wrote.

The B cells of patients with RRMS lose the ability to produce the regulatory cytokine interleukin 10. The question for the team was whether glatiramer acetate would normalize cytokine production.

They found that the therapy affects B-cell function but that “the exact contribution of B-cell-derived cytokines in MS is not clear.” The researchers said they suspect that the drug affects the pathway of B-cell activation.

“It stands to reason that glatiramer acetate therapy may alter pathways that are important for integrating these activation signals and other key immunologic genes that are modulated by glatiramer acetate therapy,” they wrote.

Additionally, they believe that glatiramer acetate therapy modulates B-cell responses to the protein CD40L, a key player in immune response.

In the study, they found that when B-cells were cultured with low-dose CD40L, “B-cell proliferation from the healthy donors, treatment-naïve patients, and glatiramer acetate patients were not significantly different.” But when high-dose C40L was used in the culture, B cells from glatiramer acetate and treatment-naïve patients proliferated significantly less compared with those of the healthy donors and treatment-naïve patients. The B cells from patients getting the drug were less responsive to the high-dose CD40L, however, suggesting these patients may have a defect in their ability to respond to high-dose CD40L.