Andrew J Worth1,2,3, Sankha S Basu1,3, Eric C Deutsch3,4, Wei-Ting Hwang2,5, Nathaniel W Snyder1,6, David R Lynch4, Ian A Blair1,2,3. 1. Center of Excellence in Environmental Toxicology, University of Pennsylvania, Philadelphia, PA 19104, USA. 2. Penn SRP Center, University of Pennsylvania, Philadelphia, PA 19104, USA. 3. Department of Systems Pharmacology & Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. 4. Departments of Neurology & Pediatrics, The Children's Hospital of Philadelphia & the Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. 5. Department of Biostatistics & Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. 6. AJ Drexel Autism Institute, Drexel University, Philadelphia, PA 19104, USA.
Abstract
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.
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.
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