Positron Emission Tomography Reveals Increased Myocardial Glucose Uptake in a Subset of Friedreich Ataxia Patients

Authors

• R Mark Payne
• Thomas M O'Connell
• P Melanie Pride
• Gregg R Wagner
• George J Eckert
• Tiffany R Johnson
• Weinian Shou
• Gary D Hutchins

Language

English

Publication Date

10-24-2025

Journal

Scientific Reports

DOI

10.1038/s41598-025-21330-w

PMID

41136607

PMCID

PMC12552483

PubMedCentral® Posted Date

10-24-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Why some but not all patients with the rare disease Friedreich ataxia (FRDA) are at increased risk of poor cardiovascular outcome and death is unclear and unpredictable. We investigated the hypothesis that mitochondrial dysfunction in FRDA leads to altered patterns of myocardial metabolic substrate utilization. We recruited 5 healthy controls (Ctl) and 11 FRDA participants. All underwent fasting myocardial positron emission tomography (PET scan) with 15O–H2O, 18F-FDG, and 11C-Palmitate. We conducted cardiac transcriptomics on mice with ablation of the Frda gene in heart to explore mechanisms of fuel substrate utilization. Five (45%) FRDA participants had an LV mass index (LVMi) less than 51 g/m2.7 (Group I), and 6 (55%) FRDA participants had an LVMi greater than this (Group II). 73% (8/11) of all FRDA participants had evidence of increased myocardial FDG uptake relative to controls. All of Group II had FDG/Palmitate utilization ratios > 95% versus controls, as well as cTnI leak (p = 0.007) when compared to Ctl (p = 0.008) or Group I (p = 0.022). RNA transcriptomics from FRDA mouse heart showed upregulation of genes for glucose uptake and glycolysis with decreased genes associated with mitochondrial energy production. In summary, PET scan identified 2 metabolically distinct subclasses of FRDA cardiomyopathy. FRDA participants with an LVMi greater than 51 g/m2.7 had greater FDG uptake than those with an LVMi less than 51 g/m2.7, or Ctl, and this correlated with LV systolic and diastolic dysfunction. Supporting this finding, gene expression in the FRDA mouse heart shifts to favor glycolysis with decreased mitochondrial energy production.

Keywords

Friedreich Ataxia, Humans, Positron-Emission Tomography, Glucose, Myocardium, Male, Female, Mice, Animals, Adult, Fluorodeoxyglucose F18, Middle Aged, Case-Control Studies, Cardiovascular biology, Translational research

Published Open-Access

yes

Recommended Citation

Payne, R Mark; O'Connell, Thomas M; Pride, P Melanie; et al., "Positron Emission Tomography Reveals Increased Myocardial Glucose Uptake in a Subset of Friedreich Ataxia Patients" (2025). Faculty, Staff and Student Publications. 955.
https://digitalcommons.library.tmc.edu/uthshis_docs/955