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Investigators at the Johannes Gutenberg University in Mainz, Germany, and colleagues have reported success in reducing inflammation and disease activity in mouse models of MS by injecting messenger RNA that had been manipulated to deliver to the immune system the codes of molecular targets thought to be involved in the development of MS.

• The goal is to induce immune tolerance to the targets (“antigens”) – in this case components of the protective myelin coating that is damaged by immune attacks in MS – without compromising normal protective immune responses.
• The researchers delivered a modified messenger RNA, containing the code for part of a myelin component, to the mice after the MS-like disease EAE (experimental autoimmune encephalomyelitis) had begun. They reported less severe disease than would normally occur.
• Analysis of immune system activity indicated reduced inflammation and an uptick of regulatory cells capable of tamping down immune attacks specific to myelin. Importantly, they also found that the immune response to a non-myelin target was unchanged.
• Various forms of mRNA are being explored as therapies for diseases in humans. These researchers hope that delivering coded instructions for myelin antigens using their modified mRNA will increase chances of success and lead to a future new therapy for people with MS that may spare the beneficial activities of the immune system while stopping MS-specific immune activity.

Comment: There is considerable interest in this study because it uses similar technology to the Pfizer-BioNT COVID-19 vaccine, but applied to a different purpose. This early result in mice will require considerable testing before this approach can lead to clinical trials in people. 

“A noninflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis,” by Drs. Christina Krienke, Ugur Sahin, and colleagues, was published in Science on January 8, 2021 (Vol. 371, Issue 6525, pp. 145-153).