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Evaluating Treatment Efficacy in a Mouse Model of Enterovirus D68-Associated Paralytic Myelitis.
J Infect Dis. 2017 12 05; 216(10):1245-1253.JI

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.

Authors+Show Affiliations

Medical Scientist Training Program. Neuroscience Program.Department of Neurology.Department of Neurology. Department of Medicine. Department of Immunology and Microbiology, University of Colorado School of Medicine Aurora.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

28968718

Citation

Hixon, Alison M., et al. "Evaluating Treatment Efficacy in a Mouse Model of Enterovirus D68-Associated Paralytic Myelitis." The Journal of Infectious Diseases, vol. 216, no. 10, 2017, pp. 1245-1253.
Hixon AM, Clarke P, Tyler KL. Evaluating Treatment Efficacy in a Mouse Model of Enterovirus D68-Associated Paralytic Myelitis. J Infect Dis. 2017;216(10):1245-1253.
Hixon, A. M., Clarke, P., & Tyler, K. L. (2017). Evaluating Treatment Efficacy in a Mouse Model of Enterovirus D68-Associated Paralytic Myelitis. The Journal of Infectious Diseases, 216(10), 1245-1253. https://doi.org/10.1093/infdis/jix468
Hixon AM, Clarke P, Tyler KL. Evaluating Treatment Efficacy in a Mouse Model of Enterovirus D68-Associated Paralytic Myelitis. J Infect Dis. 2017 12 5;216(10):1245-1253. PubMed PMID: 28968718.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evaluating Treatment Efficacy in a Mouse Model of Enterovirus D68-Associated Paralytic Myelitis. AU - Hixon,Alison M, AU - Clarke,Penny, AU - Tyler,Kenneth L, PY - 2017/08/03/received PY - 2017/09/07/accepted PY - 2017/10/3/pubmed PY - 2017/12/23/medline PY - 2017/10/3/entrez KW - Enterovirus D68 KW - acute flaccid myelitis KW - mouse model KW - paralysis KW - therapies SP - 1245 EP - 1253 JF - The Journal of infectious diseases JO - J. Infect. Dis. VL - 216 IS - 10 N2 - 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. SN - 1537-6613 UR - https://www.unboundmedicine.com/medline/citation/28968718/Evaluating_Treatment_Efficacy_in_a_Mouse_Model_of_Enterovirus_D68_Associated_Paralytic_Myelitis_ L2 - https://academic.oup.com/jid/article-lookup/doi/10.1093/infdis/jix468 DB - PRIME DP - Unbound Medicine ER -