Acute flaccid myelitis, or AFM, is a rare but devastatingly debilitating neurologic disease in children caused by a respiratory viral infection. The condition affects the nervous system, in particular the gray matter of the spinal cord which can result in sudden arm or leg weakness, a loss of reflexes, and a degeneration of muscle tone. Children affected may also experience difficulty with swallowing, neck or back pain, and drooping eyelids.
The disease, which bears symptomatic similarities to polio, has been confirmed in over 600 children in the United States since case tracking was initiated in 2014. Over 90 percent of AFM cases were reported in young children and cases appear to be on the rise. Cases often tend to peak between August and October, when respiratory viral infections often peak.
A collaborative effort between researchers at Vanderbilt, Purdue, and the University of Wisconsin-Madison have recently made a significant breakthrough in the hunt for ways to treat AFM, as described in a publication in Science Immunology. The team looked to natural immune responses for answers, identifying human monoclonal antibodies that bind specifically to the respiratory virus responsible for AFM. First identified in California in 1962, enterovirus D68 (EV-D68) belongs to a family of 100 other non-polio enteroviruses.
Antibodies are Y-shaped proteins produced by immune cells called plasma cells and play a critical role in the neutralization of invading pathogens such as bacteria and viruses. Scientists at Vanderbilt began with taking samples of these antibody-producing immune cells from children who had been infected by EV-D68. Specialized techniques were used to grow the cells under laboratory conditions and isolate the antibodies capable of most strongly binding EV-D68 and inactivating it. These, like other clinically-approved antibody-based drugs on the market, have the potential to be used therapeutically.
Next, the structure of the antibodies was analyzed by teammates at Purdue, which allowed scientists to identify the precise sites on the virus recognized by these antibodies. Of the panel of anti-enterovirus antibodies discovered, one molecule was shown to be particularly potent at resisting infection. In a series of experiments in mice, this antibody protected the mice from symptoms including paralysis when administered prior to or subsequent to EV-D68 infection.
Further validation and clinical translation are planned as future steps for the research targeting AFM, for which there is currently no treatment or cure.
"We were excited to isolate potent human antibodies that inhibit this devastating polio-like virus, and these studies will form the basis for taking them forward to clinical trials," said Dr. James Crowe, director of the Vanderbilt Vaccine Center.