Laquinimod Ups Brain-Derived Neurotrophic Factor in MS
(HealthDay News) - Treatment with laquinimod is associated with a significant increase in the serum levels of brain-derived neurotrophic factor (BDNF) in patients with multiple sclerosis (MS), and increases the severity of experimental autoimmune encephalomyelitis (EAE) in mice with brain-derived neurotrophic factor deficiency vs. wild-type mice, according to a study published online December 8, 2011 in The American Journal of Pathology.
Jan Thöne, MD (of the Ruhr-University Bochum in Germany) and colleagues evaluated the potential neuroprotective capacity of laquinimod via modulation of BDNF. Blood samples from 203 patients with multiple sclerosis who were treated with laquinimod were analyzed for the expression of BDNF. A conditional BDNF knockout strain, which lacks BDNF expression in myeloid cells and T cells (LLF mice), was used to investigate the effect of laquinimod in EAE.
The investigators found that, compared with baseline and placebo-treated patients, patients with MS who were treated with laquinimod showed a significant and persistent increase in BDNF serum levels. Compared with wild-type mice, LLF mice treated with laquinimod exhibited a more severe EAE disease course. An anti-inflammatory cytokine pattern was secreted by laquinimod-treated wild-type monocytes, but not by untreated wild-type monocytes or treated LLF monocytes. The disease course was ameliorated by adoptive transfer of laquinimod-stimulated monocytes into mice with EAE.
"Consistent with immunomodulatory properties, laquinimod skewed monocytes toward a regulatory phenotype and also acted via modulation of BDNF, which may contribute to neuroprotection in MS patients," the authors write.
One author disclosed financial ties to Teva Pharmaceuticals, which funded the study and provided laquinimod and serum samples from the phase II laquinimod study 5062 clinical trial.