Glutathione Levels Decreased in the Motor Cortex of Patients with Amyotrophic Lateral Sclerosis

Glutathione (GSH) levels are decreased in the motor cortex of patients with amyotrophic lateral sclerosis (ALS) (also known as Lou Gehrig’s disease), suggesting that oxidative stress may play a direct role in the neurodegeneration that occurs in ALS, according to research presented at the 65^th Annual Meeting of the American Academy of Neurology.

ALS is characterized by progressive neuromuscular failure, caused by the degeneration of both upper motor neurons in the motor cortex and in the lower motor neurons that connect the spinal cord and brain stem to muscle fibers. This neurodegeneration leads to muscle denervation and atrophy.

ALS affects 1 to 2 per 100,000 worldwide, and the cause of most cases is unknown. However, preclinical studies have suggested that oxidative stress, arising from an imbalance of reactive oxygen species production and the body’s ability to repair the damage, may play a role an important role in the pathogenesis of ALS. The nervous system, immune system, lungs, and gastrointestinal system are particularly affected by the state of the glutathione system.

Glutathione is the primary endogenous antioxidant produced by the cells, which neutralizes free radicals and reactive oxygen species. Studies of potent antioxidants that penetrate the blood-brain barrier into the central nervous system hold promise.

Nora Weiduschat, MD, MH, of Weill Cornell Medical College in New York City, and colleagues conducted a cross-sectional, observational study involving 12 ALS patients and 11 age-matched healthy volunteers as controls to compare in vivo motor cortex levels of GSH, as measured by magnetic resonance spectroscopy (MRS) methods.The specific imaging technique used was previously described by Shungu et al. (NMR Biomed. 2012;25:1073-1087). In addition to GSH, levels of N-acetylaspartate (NAA), lactate, gamma aminobutyric acid (GABA), and glutamate were also obtained.

A statistically significant reduction in motor cortex levels of GSH was found in ALS patients compared with healthy controls. Additionally, NAA levels were also significantly lower in ALS patients compared with controls. No other between-group differences in metabolites were found, and age did not affect the GSH or NAA levels observed in this study.

“To our knowledge, this is the first study to show decreased cortical GSH in vivo in ALS, directly implicating oxidative stress. Our finding of decreased NAA/Cr in ALS is consistent with prior MRS studies and suggests neurodegeneration. Further studies are warranted to investigate MRS measurements of GSH as potential noninvasive biomarker for diagnosis and therapy monitoring,” the authors concluded.

Several authors reported potential financial conflicts of interest.