Metabolomics of cerebrospinal fluid from humans treated for rabies

Aifric O'Sullivan, Rodney E. Willoughby, Darya Mishchuk, Brisa Alcarraz, Cesar Cabezas-Sanchez, Rene Edgar Condori, Dan David, Rafael Encarnacion, Naaz Fatteh, Josefina Fernandez, Richard Franka, Sara Hedderwick, Conall McCaughey, Joanne Ondrush, Andres Paez-Martinez, Charles Rupprecht, Andres Velasco-Villa, Carolyn M. Slupsky

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


Rabies is a rapidly progressive lyssavirus encephalitis that is statistically 100% fatal. There are no clinically effective antiviral drugs for rabies. An immunologically naiv e 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.

Original languageEnglish
Pages (from-to)481-490
Number of pages10
JournalJournal of Proteome Research
Issue number1
StatePublished - 4 Jan 2013


  • Cerebrospinal fluid
  • Metabolomics
  • NMR spectroscopy
  • Rabies


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