Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system where myelin loss, which eventually leads to neurodegeneration, is caused by infiltration of various immune cells. The first line immune reaction includes microglia, coming from the brain itself, and macrophages, which originate from the blood. Over the past 6 years we investigated whether immune modulation of microglia and/or macrophages by the cytokine, interleukin 13 (IL13), could have an effect on MS disease progression. Our pre-clinical studies in an MS mouse model demonstrated that local IL13-production could lead to reduced loss of myelin and myelin-producing cells. Now, our next step is to determine the potency of IL13 on human brain tissue grown from stem cells in the laboratory.

Due to the current understanding that multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS), where mononuclear cell infiltration is a major contributor to demyelination, gliosis, axonal damage and loss of neuronal function, we investigated over the past 6 years whether immune modulation with interleukin (IL)13 might ameliorate disease progression. While our pre-clinical studies in the cuprizone-induced inflammation/demyelination mouse model for human MS have demonstrated proof-of-principle, we do not know whether human microglia and macrophages are equally susceptible to IL13 in the pro-inflammatory MS environment. Using advanced human induced pluripotent stem cell-derived 3D cell culture models, we aim to provide further pre-clinical rationale for the use of IL13 as a novel approach in advanced stage MS.