A team funded by the National MS Society and the MS Society of Canada reports that using a novel strategy to block harmful effects of the brain chemical glutamate can protect the nervous system from damage in mice with MS-like disease. Further research is needed to determine whether this approach would be safe and beneficial in people who have MS. FangLiu, MD, PhD (University of Toronto) and colleagues report their results in the Annals of Clinical and Translational Neurology (Article first published online: February 19, 2015).
Background: The myelin sheath that surrounds and protects nerve fibers is damaged and destroyed in the brain and spinal cord by MS. Nerve fibers are also destroyed, leading to the long-term disability that is experienced by people with progressive MS. An important unmet need in MS is finding ways to protect the nervous system from damage caused by MS and stop or reverse the progression of disability.
A normal brain chemical called glutamate, which is necessary for transmitting nerve signals, may play a role in nerve cell death in MS. But developing a strategy to block glutamate completely is not feasible as a treatment for MS because it is critical for normal brain function. Fang Liu, MD, PhD, and team investigated whether a small fragment of protein, or peptide, known as G-Gpep can limit glutamate-initiated nerve damage by selectively blocking a specific interaction between two proteins with which glutamate interacts (namely, the “GluR2-GAPDH complex”) in nerve cells.
The Study: The team first tested whether the GluR2-GAPDH complex is altered in the brains of people with MS and in a mouse model of MS. They found that this protein complex was present at significantly higher than normal levels in both.
Next, they tested the effectiveness of G-Gpep in reversing neurological symptoms in mice with EAE, an MS-like disease. G-Gpep greatly improved neurological function, reduced nerve cell death, myelin damage, and nerve fiber damage in the spinal cord and increased the survival of cells that make myelin. G-Gpep did not appear to suppress glutamate completely or block nerve impulse transmission.
Comment: The results of this early research indicate that G-Gpep warrants further study as a possible mode of protecting the nervous system from damage. Additional research and testing is required to develop this peptide into a potential therapy that would be safe and effective in people with MS. Dr. Liu is one of many researchers funded by the National MS Society who are exploring mechanisms that drive injury to the brain and spinal cord to expose new potential therapeutic targets for treating progressive MS.
Read more about research to stop progressive MS.
Note: A portion of this research relied on the study of brain tissue obtained from people with MS who had donated their brains to MS research through the National MS Society-supported MS tissue bank in Los Angeles. Learn more about planning in advance to donate this precious gift to help MS research.