News Blocking Molecule Evident in Excess in MS Patients Treats Mice with SPMS-like Disease, Study Reports Blocking Molecule Evident in Excess in MS Patients Treats Mice with SPMS-like Disease, Study Reports by Ana Pena PhD | October 29, 2018 Share this article: Share article via email Copy article link Blocking a molecule that is overly abundant in the nervous system of multiple sclerosis (MS) patients, and has been linked to nerve cell damage in animals, worked to significantly ease inflammation, demyelination, and neurodegeneration in mouse models of secondary progressive MS (SPMS), a study reports. Treatment to inhibit this molecule also helped the SPMS mice recover damaged neural networks and motor ability. The study “Inhibiting repulsive guidance molecule-a suppresses secondary progression in mouse models of multiple sclerosis” was published in the journal Cell Death & Disease. Earlier research demonstrated that repulsive guidance molecule-a (RGMa) is overabundant in the central nervous system of MS patients. This molecule is expressed at the cell membrane and is critical for the formation of neural networks, but it also works to inhibit nerve fiber (axon) growth and affects immune regulation. Studies done in mouse models of MS showed that RGMa contributes to the progression of MS-like disease, promoting inflammation and nerve cell death. Importantly, treating these animal models with an antibody that blocks RGMa was seen to ease disease manifestations. Based on this knowledge, a team of researchers at Osaka University, in Japan, wondered if this treatment would also confer benefits in mouse models of SPMS. The researchers used a mouse model of SPMS — the non-obese diabetic mice with experimental autoimmune encephalomyelitis, the NOD-EAE model “that closely resembles SPMS,” they noted. Mice were divided into three groups: two treated intravenously with a humanized antibody targeting RGMa at two different doses, and one given a related antibody with no therapeutic effect to serve as controls. Results showed that the humanized anti-RGMa antibody was able to decrease the expression of RGMa in the spinal cord of the mice, and reduce the proportion of mice with disease progression. Microscopic analysis of spinal cord tissue also showed that anti-RGMa suppressed inflammation, reducing the infiltration and activation of immune cells, and prevented the loss of myelin (demyelination) and death of nerve cells. “As [an] impaired neural network is responsible for the neurological symptoms under SPMS,” the researchers investigated if anti-RGMa enhanced the regeneration of the neuronal network, leading to functional recovery. They saw that anti-RGMa antibody treatment promoted a significantly faster motor recovery in mice with spinal cord injury. This positive outcome was linked to the antibody’s ability to trigger axonal sprouting in response to the injury — the growth of nerve fibers that help regenerate the damaged tissue and re-establish neuronal networks. Overall, the team concluded that the “humanized anti-RGMa antibody prevented the progression of motor deficits in NOD-EAE by suppressing inflammation, demyelination, and neurodegeneration. Moreover, it promoted the functional recovery presumably by promoting the axonal rewiring.” According to the researchers, “RGMa is implicated in not only inflammation, but also neurodegeneration and neuroregeneration in MS. Thus, humanized anti-RGMa antibody is expected to be the effective treatment for SPMS.” Print This Page About the Author Ana Pena PhD Ana is a molecular biologist with a passion for communication and discovery. As a science writer, her goal is to provide readers, in particular patients and healthcare providers, with clear and quality information about the latest medical advances. Ana holds a Ph.D. in Biomedical Sciences from the University of Lisbon, Portugal, where she specialized in infectious diseases, epigenetics, and gene expression. Tags demyelination, EAE, neurodegeneration, SPMS
April 17, 2024 News by Steve Bryson, PhD NfL blood levels predict CIS to MS conversion: Clinical trial data
April 16, 2024 News by Marisa Wexler, MS Patients deem AI-based ChatGPT more empathetic than neurologists