Fighting friendly fire with fire: an antibody for

image: Anti-RGMa antibody treatment improves NMO pathophysiology
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Osaka, Japan – Autoimmune diseases are the molecular equivalent of “friendly fire”: the body attacks itself instead of harmful invaders. Now, Japanese researchers have discovered that interrupting the complex interaction between different types of immune cells can help prevent the damage caused by this friendly fire in a type of autoimmune disease.

In a study published this month in Annals of NeurologyOsaka University researchers have found that treatment with an antibody directed against a protein called repulsive guidance molecule-a (RGMa) significantly improves symptoms of neuromyelitis optica, a devastating autoimmune disease, in a model rat experimental.

Neuromyelitis optica (NMO) is an inflammatory disease that can cause pain, paralysis and even death. In most cases, NMO is caused by antibodies the body develops against a protein called aquaporin-4 (AQP4). These anti-AQP4 antibodies leak into the tissues at sites of nerve damage which also show a massive accumulation of neutrophils. This buildup of neutrophils is associated with the death of cells called astrocytes, which ultimately causes symptoms of NMO.

“We recently found that injecting rats with an antibody against RGMa can reduce the severity of NMO symptoms,” says the study’s lead author, Shosuke Iwamoto. “However, it was still unclear how this treatment worked mechanically, whether by affecting AQP4, astrocytes, or another factor.”

To address this issue, the researchers used a clinically relevant rat model of NMO to test the effects of the anti-RGMa antibody on disease symptoms, as well as gene and protein expression.

“Our findings revealed a novel molecular mechanism of NMO pathophysiology in which RGMa stimulates macrophages to attract neutrophils to lesions, where they kill astrocytes,” explains lead author Toshihide Yamashita.

Importantly, treating rats with an anti-RGMa antibody prevented these effects, resulting in fewer neutrophils around nerve damage, less astrocyte destruction, and fewer symptoms such as movement problems and pain.

“Our results suggest that anti-RGMa antibodies may represent an effective therapeutic strategy for NMO-associated neuropathic pain and motor deficits in patients with NMO,” says Iwamoto.

Since the severity of acute NMO attacks greatly affects patients’ long-term outcomes, treatments targeting RGMa that help reduce attack severity or improve the recovery process are crucial to improving their quality of life. Treatment with an anti-RGMa antibody could even potentially be useful in preventing relapses of NMO in the chronic stage of the disease.

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The article, “RGMa signal in macrophages induces neutrophil-related astrocytopathy in NMO,” was published in Annals of Neurology at DOI:

Funders: Japan Society for the Promotion of Science, Japan Agency for Medical Research and Development

About Osaka University

Osaka University was founded in 1931 as one of Japan’s Seven Imperial Universities and today is one of Japan’s leading comprehensive universities with a wide range of disciplines. This strength is coupled with a singular desire for innovation that extends throughout the scientific process, from basic research to the creation of applied technologies with positive economic spinoffs. Its commitment to innovation has been recognized in Japan and around the world, being named Japan’s most innovative university in 2015 (Reuters 2015 Top 100) and one of the world’s most innovative institutions in 2017 (Innovative Universities and the Nature Index Innovation 2017). Today, Osaka University leverages its role as a designated national university society selected by the Ministry of Education, Culture, Sports, Science and Technology to contribute innovation for human well-being, sustainable development of society and social transformation.

Website: https://resou.osaka-u.ac.jp/en


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