Researchers Identify New Potential Targets for Stopping Nerve Loss in MS

Researchers from the Gladstone Institutes, the University of California, San Francisco, and others reported results of studies aimed at mapping out processes that contribute to nerve degeneration in progressive MS and other disorders. They also screened compounds with potential to interfere with nerve loss. This work was supported in part by the National MS Society.

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• The team focused on activated innate immune cells in the brain and spinal cord called macrophages and microglia, which produce molecules that induce a condition called oxidative stress. Oxidative stress is the result of an imbalance of harmful molecules called “free radicals.” These are normally rendered harmless by antioxidants produced by the body, but this antioxidative process may not work correctly in MS.
• Using advanced technologies, the team developed an “atlas” that profiles the landscape of complex interactions of these innate immune cells in the brain and gene activities involved in oxidative stress. This atlas uncovered new interactions and pathways that have potential to be targeted to protect the nervous system from degenerative processes.
• As a proof of principle, they targeted one of the pathways by administering an anti-tumor compound called acivicin to lab mice with MS-like disease. Even in mice with longer-term disease, this compound reduced oxidative stress and ongoing nervous system damage.
• Although acivicin itself is too toxic to be developed for the treatment of MS or other neurodegenerative disorders, this work represents an important step forward in identifying “druggable” pathways that may lead to the development of treatments to stop nerve loss and progression in MS. 

“Transcriptional profiling and therapeutic targeting of oxidative stress in neuroinflammation,” by Drs. Andrew Mendiola, Katerina Akassoglou and collaborators, was published early online on April 13, 2020 in Nature Immunology. Read more details on the Gladstone’s website Read the scientific abstract