Treatment with immunosuppressive and anti-inflammatory agents delays onset of canine genetic narcolepsy and reduces symptom severity

Experimental Neurology
Lisa N BoehmerJerome M Siegel

Abstract

All Doberman pinschers and Labrador retrievers homozygous for a mutation of the hypocretin (orexin) receptor-2 (hcrtr2) gene develop narcolepsy under normal conditions. Degenerative changes and increased display of major histocompatibility complex class II antigens have been linked to symptom onset in genetically narcoleptic Doberman pinschers. This suggests that the immune system may contribute to neurodegenerative changes and narcoleptic symptomatology in these dogs. We therefore attempted to alter the course of canine genetic narcolepsy, as an initial test of principle, by administering a combination of three immunosuppressive and anti-inflammatory drugs chosen to suppress the immune response globally. Experimental dogs were treated with a combination of methylprednisolone, methotrexate and azathioprine orally starting within 3 weeks after birth, and raised in an environment that minimized pathogen exposure. Symptoms in treated and untreated animals were quantified using the food elicited cataplexy test (FECT), modified FECT and actigraphy. With drug treatment, time to cataplexy onset more than doubled, time spent in cataplexy during tests was reduced by more than 90% and nighttime sleep periods were consolidated. Short-term...Continue Reading

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Citations

Sep 5, 2008·Journal of Neurology·Giuseppe PlazziPasquale Montagna
Sep 23, 2006·Nature Clinical Practice. Neurology·Jerome M Siegel, Lisa N Boehmer
May 22, 2008·Genetics·Federico C F CalboliDavid J Balding
May 4, 2007·Sleep Medicine·Michael Thorpy
Dec 14, 2004·Lancet·Merrill S Wise
Nov 11, 2005·The FEBS Journal·Luis de Lecea, J Gregor Sutcliffe
Jan 31, 2020·Current Treatment Options in Neurology·Maria Pia GiannoccaroFabio Pizza
Aug 26, 2017·Neurology. Neuroimmunology and Neuroinflammation·Rannveig VisteStine Knudsen
Jun 30, 2010·Revista brasileira de psiquiatria : orgão oficial da Associação Brasileira de Psiquiatria, Asociación Psiquiátrica de la América Latina·Flávio AlóeStella Márcia Azevedo Tavares
Jul 19, 2019·Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova·A V MedvedevaM G Poluektov
Feb 9, 2021·Topics in Companion Animal Medicine·Alejandra MondinoGiancarlo Vanini
Jan 2, 2021·Sleep Medicine·Giuliano da Paz OliveiraFernando Morgadinho Santos Coelho

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