Metabolomics of cerebrospinal fluid from humans treated for rabies. J Proteome Res 2013 Jan 04;12(1):481-90
Date
11/21/2012Pubmed ID
23163834Pubmed Central ID
PMC4824192DOI
10.1021/pr3009176Scopus ID
2-s2.0-84874060602 (requires institutional sign-in at Scopus site) 46 CitationsAbstract
Rabies is a rapidly progressive lyssavirus encephalitis that is statistically 100% fatal. There are no clinically effective antiviral drugs for rabies. An immunologically naïve teenager survived rabies in 2004 through improvised supportive care; since then, 5 additional survivors have been associated with use of the so-called Milwaukee Protocol (MP). The MP applies critical care focused on the altered metabolic and physiologic states associated with rabies. The aim of this study was to examine the metabolic profile of cerebrospinal fluid (CSF) from rabies patients during clinical progression of rabies encephalitis in survivors and nonsurvivors and to compare these samples with control CSF samples. Unsupervised clustering algorithms distinguished three stages of rabies disease and identified several metabolites that differentiated rabies survivors from those who subsequently died, in particular, metabolites related to energy metabolism and cell volume control. Moreover, for those patients who survived, the trajectory of their metabolic profile tracked toward the control profile and away from the rabies profile. NMR metabolomics of human rabies CSF provide new insights into the mechanisms of rabies pathogenesis, which may guide future therapy of this disease.
Author List
O'Sullivan A, Willoughby RE, Mishchuk D, Alcarraz B, Cabezas-Sanchez C, Condori RE, David D, Encarnacion R, Fatteh N, Fernandez J, Franka R, Hedderwick S, McCaughey C, Ondrush J, Paez-Martinez A, Rupprecht C, Velasco-Villa A, Slupsky CMAuthor
Rodney E. Willoughby MD Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdolescentAdult
Antiviral Agents
Female
Gene Expression Profiling
Humans
Male
Metabolomics
Rabies
Rabies Vaccines
Rabies virus
