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Lookup NU author(s): Professor Michela GuglieriORCiD, Laura Behar, Dr Marianela Schiava, Meredith JamesORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2024 The Author(s). The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.Abstract: Duchenne muscular dystrophy (DMD) results in a progressive loss of functional skeletal muscle mass (MM) and replacement with fibrofatty tissue. Accurate evaluation of MM in DMD patients has not previously been available. Our objective was to measure MM using the D3creatine (D3Cr) dilution method and determine its relationship with strength and functional capacity in patients with DMD over a wide range of ages. Subjects were recruited for participation in a 12 month, longitudinal, observational study. Here, we report the baseline data. A 20 mg dose of D3Cr dissolved in water was ingested by 92 patients with DMD (ages 4–25 years) followed later with a fasting urine sample. Enrichment of D3creatinine was determined by liquid chromatography-mass spectrometry analysis. The North Star Ambulatory Assessment (NSAA) total score was determined for ambulatory participants, and the Performance of Upper Limb (PUL 2.0) total score and grip strength for all participants. We observed a significant age-associated increase in body weight along with a substantial decrease in MM/body weight (%MM). MM and %MM were associated with PUL score (r = 0.517, P < 0.0001 and r = 0.764, P < 0.0001 respectively). The age-associated decrease in MM and %MM was strongly associated with ambulatory status. We observed very little overlap in %MM between ambulant and non-ambulant subjects, suggesting a threshold of 18–22% associated with loss of ambulation. MM is substantially diminished with advancing age and is highly related to clinically meaningful functional status. The D3Cr dilution method may provide a biomarker of disease progression and therapeutic efficacy in patients with DMD or other neuromuscular disorders. (Figure presented.). Key points: The non-invasive D3creatine dilution method provides novel data on whole body functional muscle mass (MM) in a wide range of ages in patients with DMD and reveals profoundly low functional MM in older non-ambulant patients. The difference in %MM between ambulant and non-ambulant subjects suggests a threshold for loss of ambulatory ability between 18 and 22% MM. The data suggest that as functional MM declines with age, maintaining a lower body weight may help to conserve ambulatory ability.
Author(s): Evans WJ, Hellerstein M, Butterfield RJ, Smith E, Guglieri M, Katz N, Nave B, Branigan L, Thera S, Vordos KL, Behar L, Schiava M, James MK, Field T, Mohammed H, Shankaran M
Publication type: Article
Publication status: Published
Journal: Journal of Physiology
Year: 2024
Pages: epub ahead of print
Online publication date: 31/08/2024
Acceptance date: 15/08/2024
Date deposited: 10/09/2024
ISSN (print): 0022-3751
ISSN (electronic): 1469-7793
Publisher: John Wiley and Sons Inc
URL: https://doi.org/10.1113/JP287069
DOI: 10.1113/JP287069
Data Access Statement: Data will be made available upon completion of all aspects of the longitudinal study and publication of results. Access of data may be made through contact with William Evans (william.evans@berkeley.edu)
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