Metabolomic analysis and signatures in motor neuron disease.
Motor neuron diseases (MND) are a heterogeneous group of disorders that includes amyotrophic lateral sclerosis (ALS) and result in death of motor neurons. These diseases may produce characteristic perturbations of the metabolome, the collection of small-molecules (metabolites) present in a cell, tissue, or organism. To test this hypothesis, we used high performance liquid chromatography followed by electrochemical detection to profile blood plasma from 28 patients with MND and 30 healthy controls. Of 317 metabolites, 50 were elevated in MNDpatients and more than 70 were decreased (p < 0.05). Among the compounds elevated, 12 were associated with the drug Riluzole. In a subsequent study of 19 subjects with MND who were not taking Riluzole and 33 healthy control subjects, six compounds were significantly elevated in MND, while the number of compounds with decreased concentration was similar to study 1. Our data also revealed a distinctive signature of highly correlated metabolites in a set of four patients, three of whom had lower motor neuron (LMN) disease. In both datasets we were able to separate MND patients from controls using multivariate regression techniques. These results suggest that metabolomic studies can be used to ascertain metabolic signatures of disease in a non-invasive fashion. Elucidation of the structures of signature molecules in ALS and other forms of MND should provide insight into aberrant biochemical pathways and may provide diagnostic markers and targets for drug design.
Rozen
Steve
S
Metabolon Inc., 800 Capitola Dr., Research Triangle Park, NC 27709.
Cudkowicz
Merit E
ME
Bogdanov
Mikhail
M
Matson
Wayne R
WR
Kristal
Bruce S
BS
Beecher
Chris
C
Harrison
Scott
S
Vouros
Paul
P
Flarakos
Jimmy
J
Vigneau-Callahan
Karen
K
Matson
Theodore D
TD
Newhall
Kristyn M
KM
Beal
M Flint
MF
Brown
Robert H
RH
Kaddurah-Daouk
Rima
R