Antioxidant precursor molecule could improve brain function in patients with MS

Summary: Multiple sclerosis patients who received N-acetylcysteine treatments had improvements in metabolism in brain areas associated with cognition and attention.

Source: Thomas Jefferson University

N-acetylcysteine (NAC) is a naturally occurring molecule that replenishes antioxidants and shows improved brain metabolism and self-reported improvements in cognitive function in patients with multiple sclerosis, according to a study published in the journal, Frontiers in Neurology.

The study found improvements in brain metabolism, particularly in areas that support cognition such as the frontal and temporal lobes in patients with multiple sclerosis. In addition, patients reported qualitative improvements in their cognitive and attention focusing abilities. The study was performed by the Department of Integrative Medicine and Nutritional Sciences, as well as the Departments of Neurology and Radiology, at Thomas Jefferson University.

Current treatments for multiple sclerosis are generally limited to trying to slow the progression of the disease by preventing new brain lesions from occurring. However, these approaches do not help the neurons that have already been affected by the disease process. While the primary event of multiple sclerosis results from an immunological process that targets the white matter, the actual damage to neurons may be due in large part from oxidative stress caused by the immune reaction. NAC is an oral supplement, and also comes in an intravenous form that is used to protect the liver in acetaminophen overdose. Several initial studies have shown that NAC administration increases glutathione levels in the brain. Because glutathione is an antioxidant, researchers have proposed that it could reduce the oxidative stress from the immune reaction, though it’s unclear whether it would improve the function of neurons. The current study tested this by tracking cerebral glucose metabolism on positron emission tomography (PET) brain, as a proxy for normal neuronal function.

“This study is an important step in understanding how NAC might work as a potentially new avenue for managing multiple sclerosis patients. The NAC appears to enable neurons to recover some of their metabolic function,” says senior author on the paper Daniel Monti, MD, Chairman of the Department of Integrative Medicine and Nutritional Sciences and Director of the Marcus Institute of Integrative Health at Thomas Jefferson University.

Researchers evaluated 24 patients with multiple sclerosis who continued their current treatment and were placed into two groups – the first group received a combination of oral and intravenous (IV) NAC for two months (in addition to their current treatment program); and the second group, the control patients, received only their standard-of-care treatment for multiple sclerosis for two months. Patients were not blinded. Those patients in the active group received 50mg/kg NAC intravenously once per week and 500mg NAC orally 2x per day on the non IV days.

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The study found improvements in brain metabolism, particularly in areas that support cognition such as the frontal and temporal lobes in patients with multiple sclerosis The image is in the public domain.

All patients underwent brain scanning using FDG PET imaging which measures the amount of glucose metabolism in the neurons throughout the brain. This test was used to determine the level of neuronal recovery. Patients were evaluated initially and after two months of either receiving the NAC or standard of care therapy. Patients were also evaluated clinically using several different measures of brain function and quality of life.

Compared to controls, the patients receiving NAC had significant improvements in brain metabolism in the caudate, inferior frontal gyrus, lateral temporal gyrus, and middle temporal gyrus as measured by FDG PET imaging. These areas are particularly important in supporting cognition and attention, which were both perceived by patients to be improved via self-reported questionnaires of overall health and well-being.

“This is an exciting study that suggests a natural molecule such as NAC may help improve brain metabolism and symptoms in patients with multiple sclerosis,” says corresponding author and neuro-imaging expert Andrew Newberg, MD, Professor and Director of Research at the Department of Integrative Medicine and Nutritional Sciences. The investigators hope that this research will open up new avenues of treatment for multiple sclerosis patients.

Funding: There are no conflicts of interest. The study was funded by a gift from the Marcus Foundation.

About this neuroscience research article

Source:
Thomas Jefferson University
Media Contacts:
Edyta Zielinska – Thomas Jefferson University
Image Source:
The image is in the public domain.

Original Research: Open access
“N-Acetyl Cysteine Administration Is Associated with Increased Cerebral Glucose Metabolism In Patients With Multiple Sclerosis”. DA Monti, et al.
Frontiers in Neurology doi:10.3389/fneur.2020.00088.

Abstract

N-Acetyl Cysteine Administration Is Associated with Increased Cerebral Glucose Metabolism In Patients With Multiple Sclerosis

Background: Multiple Sclerosis (MS) is an autoimmune disease marked by progressive neurocognitive injury. Treatment options affording neuroprotective effects remain largely experimental. The purpose of this proof of concept study was to explore the effects of N-acetyl-cysteine (NAC) on cerebral glucose metabolism (CMRGlu) and symptoms in patients with multiple sclerosis (MS).

Methods: Twenty-four patients with MS were randomized to either NAC plus standard of care, or standard of care only (waitlist control). The experimental group received NAC intravenously once per week and orally the other 6 days. Patients in both groups were evaluated at baseline and after 2 months (of receiving the NAC or waitlist control period) with an integrated Position Emission Tomography (PET)/ Magnetic Resonance Imaging (MRI) scanner, using 18F Fluorodeoxyglucose (FDG) to measure cerebral glucose metabolism. Following imaging evaluation at 2 months, subjects initially attributed to the standard of care arm were eligible for treatment with NAC. Clinical and symptom questionnaires were also completed initially and after 2 months.

Results: The FDG PET data showed significantly increased cerebral glucose metabolism in several brain regions including the caudate, inferior frontal gyrus, lateral temporal gyrus, and middle temporal gyrus (p < 0.05) in the MS group treated with NAC, as compared to the control group. Self-reported scores related to cognition and attention were also significantly improved in the NAC group as compared to the control group.

Conclusions: The results of this study suggest that NAC positively affects cerebral glucose metabolism in MS patients, which is associated with qualitative, patient reported improvements in cognition and attention. Larger scale studies may help to determine the clinical impact of NAC on measures of functioning over the course of illness, as well as the most effective dosage and dosage regimen.

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