Objective: The goal of this study was to use magnetic resonance spectroscopy (MRS) to test whether muscles of individuals with Parkinson’s disease (PD) possess a unique bioenergetic signature related to mitochondrial function.

Background: Diminished mitochondrial function is a hallmark of aging, and disrupted cellular energetics are evident in PD and other age-related neurodegenerative diseases. A clinically relevant, non-invasive tool for measuring mitochondrial function in patients with PD could serve as a theragnostic biomarker, facilitating the development of therapeutics targeting enhancement of mitochondrial function to slow disease progression.

Method: Quantitative physiological properties of in vivo hand muscle (FDI, first dorsal interosseus) and leg muscle (TA, Tibialis Anterior) of individuals aged 60-80 years old with PD (N=22) were compared to historical age and gender-matched controls. MRS and MR imaging were used to assess mitochondrial and cell energetic dysfunction, including maximum mitochondrial ATP production (ATPmax), energy and redox status through NAD and NADH metabolites, and muscle size. Muscle function was measured via a single muscle fatigue test.

Results: Compared to healthy older adults control data from previous studies in our lab, TA ATPmax was significantly lower in the PD cohort. In the leg, NAD/NADH ratio was statistically significantly reduced in PD. Muscle endurance and specific force was lower in both hand and leg muscle in the PD subjects.

Conclusion: Results from this pilot study contribute to a growing body of evidence that PD is a systemic metabolic disorder with disrupted cellular energetics in peripheral tissues. This study looked at individuals with mid-stage PD; future research should attempt to determine whether these results are reproducible and identify how early in the disease course the mitochondrial insufficiency begins. As a theragnostic biomarker, MRS has the potential to aid in research and therapeutic development for interventions targeting cellular energetics.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/metabolic-biomarkers-of-parkinsons-disease-in-peripheral-tissue/