Abstract Details

Title Investigating Brain Glutathione Levels in Primary Mitochondrial Disease Using Edited MR Spectroscopy

Topic General Neurology

Presentation(s) P9 - Poster Session 9 (5:00 PM-6:00 PM)

Poster/Presentation
Number 7-003

Objective Novel evaluation of brain glutathione (GSH) levels in Primary Mitochondrial Disease (PMD) patients by edited Magnetic Resonance Spectroscopy (MRS) compared to healthy controls.

Background PMD are genetic disorders presenting with neurodegeneration and metabolic strokes, linked to cellular redox imbalance and altered antioxidant status evidenced by blood GSH levels. Measurement of GSH levels in brain has never been performed.

Design/Methods Nine PMD patients and seven healthy controls were studied. Clinical data and GSH levels were measured in specific brain regions [Anterior Cingulate Cortex (ACC), left motor cortex, bilateral thalamus, cerebellum]. Regional GSH levels were compared using the Mann–Whitney U test.

Results Among 9 genetically confirmed patients (4/9 males; ages 9-35) with PMD, genetic etiologies included MT-TL1 (n=6), NUBPL, MT-TV, and MT-ND4 (n=1 each). Five patients were on N-acetylcysteine (NAC, a precursor of GSH). GSH levels for the NAC-treated patients (group 1) were 3.21-4.62 in ACC, 2.82-5.13 in motor cortex, 5.09-10.14 in thalamus, and 2.72-7.91 IU in cerebellum. Meanwhile, untreated patients (group 2, n=4) had GSH levels of 3.09-4.35 in ACC, 2.58-3.50 in motor cortex, 3.37-6.13 in thalamus, and 4.50-6.21 IU in cerebellum. In 7 controls (5/7 males; ages 11-41), GSH was 3.25-4.73 in ACC, 2.16-3.39 in motor cortex, 2.43-5.88 in thalamus, and 3.25-6.15 IU in cerebellum. NAC-treated group 1 patients showed no significant mean GSH difference from controls in ACC (p=0.68) or thalamus (p=0.56) but higher in motor cortex (p=0.042) and significantly in cerebellum (p=0.004). Untreated group 2 revealed no significant differences in ACC (p=0.57), motor cortex (p=0.44), or thalamus (p=0.44), significantly higher in cerebellum (p=0.008).

Conclusions

Preliminary results reveal that cerebellar GSH levels were higher in the NAC-treated and untreated PMD patients as compared to controls. GSH levels in the motor cortex were specifically elevated in treated patients. Active studies in a larger cohort are ongoing.

Authors/Disclosures
Sonal Sharma, MD (Children's Hospital of Philadelphia/ Division of Neurology) PRESENTER	Dr. Sharma has nothing to disclose.
Albert Q. Wu, MS	Mr. Wu has nothing to disclose.
Thuy Nguyen	Mrs. Nguyen has nothing to disclose.
Reza Abdavies	Mr. Abdavies has nothing to disclose.
Zarazuela Zolkipli-Cunningham, MBChB (The Children's Hospital of Philadelphia, Human Genetics)	Dr. Zolkipli-Cunningham has nothing to disclose.
Muhammad G. Saleh, PhD	The institution of Dr. Saleh has received research support from Children's Hospital of Phialdelphia.

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