Evaluating Treatment Efficacy in a Mouse Model of Enterovirus D68–Associated Paralytic Myelitis

• Published in: The Journal of infectious diseases 2017-12, Vol.216 (10), p.1245-1253
• Main Authors: Hixon, Alison M., Clarke, Penny, Tyler, Kenneth L.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Neutralizing - blood; Antibodies, Neutralizing - immunology; Antibodies, Viral - blood; Antibodies, Viral - immunology; Dexamethasone - administration & dosage; Disease Models, Animal; Enterovirus D, Human - immunology; Fluoxetine - administration & dosage; Immunoglobulins, Intravenous - administration & dosage; Major and Brief Reports; Mice; Myelitis - diagnosis; Myelitis - physiopathology; Myelitis - therapy; Myelitis - virology; Neutralization Tests; Paralysis - diagnosis; Paralysis - physiopathology; Paralysis - therapy; Paralysis - virology; Serotonin Uptake Inhibitors - administration & dosage; Treatment Outcome; Viral Load; VIRUSES
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jix468

A mouse model of enterovirus D68 (EV-D68) paralytic myelitis can be used to evaluate the efficacy of possible treatment options for EV-D68–associated central nervous system disease. Abstract Background Enterovirus D68 (EV-D68)–associated acute flaccid myelitis (AFM) is a devastating neurological disease for which there are no treatments of proven efficacy. The unpredictable temporal and geographic distribution of cases and the rarity of the disease make it unlikely that data from randomized controlled trials will be available to guide therapeutic decisions. We evaluated the following 3 widely used empirical therapies for the ability to reduce the severity of paralysis in a mouse model of EV-D68 infection: (1) human intravenous immunoglobulin (hIVIG), (2) fluoxetine, and (3) dexamethasone. Methods Neonatal mice were injected intramuscularly with a human 2014 EV-D68 isolate that reliably induces paralysis in mice due to infection and loss of spinal cord motor neurons. Mice receiving treatments were evaluated for motor impairment, mortality, and spinal cord viral load. Results hIVIG, which contained neutralizing antibodies to EV-D68, reduced paralysis in infected mice and decreased spinal cord viral loads. Fluoxetine had no effect on motor impairment or viral loads. Dexamethasone treatment worsened motor impairment, increased mortality, and increased viral loads. Conclusion Results in this model of EV-D68–associated AFM provide a rational basis for selecting empirical therapy in humans and establish this model as a useful system for evaluating other potential therapies.