Open AccessStable isotopes and LC–MS for monitoring metabolic disturbances in Friedreich's ataxia platelets
Author(s) -
Andrew J. Worth,
Sankha S. Basu,
Éric Deutsch,
WeiTing Hwang,
Nathaniel W. Snyder,
David R. Lynch,
Ian A. Blair
Publication year - 2015
Publication title -
bioanalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.566
H-Index - 58
eISSN - 1757-6199
pISSN - 1757-6180
DOI - 10.4155/bio.15.118
Subject(s) - ataxia , biomarker , metabolome , neurodegeneration , platelet , concomitant , in vivo , cardiomyopathy , medicine , biology , biochemistry , disease , pathology , metabolite , neuroscience , heart failure , genetics
Background: Friedreich's ataxia (FRDA) is an autosomal recessive disease with metabolic abnormalities that have been proposed to play an important role in the resulting neurodegeneration and cardiomyopathy. The inability to access the highly affected neuronal and cardiac tissues has hampered metabolic evaluation and biomarker development. Methods: Employment of a LC–MS-based method to determine whether platelets isolated from patients with FRDA exhibit differentiable metabolism compared with healthy controls. Results: Isotopologue analysis showed a marked decrease in glucose incorporation with a concomitant increase in palmitate-derived acyl-CoA thioesters in FRDA platelets compared with controls. Conclusion: Our findings demonstrate that platelets can be used as a surrogate tissue for in vivo biomarker studies to monitor new therapeutic approaches for the treatment of FRDA.