Maya Katz1, Seok Joon Won2, Youngja Park3, Adrienne Orr2, Dean P Jones3, Raymond A Swanson2, Graham A Glass2. 1. Neurology Service, San Francisco Veterans Affairs Medical Center, 4150 Clement Street, San Francisco, CA 94121, USA; Department of Neurology, University of California, San Francisco Medical Center, 675 Nelson Rising Lane, San Francisco, CA 94143, USA. Electronic address: maya.katz@ucsfmedctr.org. 2. Neurology Service, San Francisco Veterans Affairs Medical Center, 4150 Clement Street, San Francisco, CA 94121, USA; Department of Neurology, University of California, San Francisco Medical Center, 675 Nelson Rising Lane, San Francisco, CA 94143, USA. 3. Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Emory University, 615 Michael Street, Suite 205, Atlanta, GA 30322, USA.
Abstract
INTRODUCTION: Depletion of neuronal glutathione may contribute to the pathogenesis of Parkinson's disease (PD). N-acetylcysteine (NAC) can restore neuronal glutathione levels, but it has not been established whether NAC can cross the blood-brain barrier in humans. METHODS: Twelve patients with PD were given oral NAC twice daily for 2 days. Three doses were compared: 7 mg/kg, 35 mg/kg, and 70 mg/kg. NAC, cysteine, and glutathione were measured in the cerebrospinal fluid (CSF) at baseline and 90 min after the last dose. Cognitive and motor functions were assessed pre- and post-NAC administration using the Montreal Cognitive Assessment (MoCA) and the Unified Parkinson's Disease Rating Scale part III motor subscore (UPDRS-III). RESULTS: Oral NAC produced a dose-dependent increase in CSF NAC concentrations (p < 0.001), with the highest dose producing a CSF concentration of 9.26 ± 1.62 μM. There were no significant adverse events. NAC had no acute effect on motor or cognitive function. CONCLUSION: Orally administered NAC produces biologically relevant CSF NAC concentrations at doses that are well tolerated. The findings support the feasibility of NAC as a potential disease-modifying therapy for PD. Published by Elsevier Ltd.
INTRODUCTION: Depletion of neuronal glutathione may contribute to the pathogenesis of Parkinson's disease (PD). N-acetylcysteine (NAC) can restore neuronal glutathione levels, but it has not been established whether NAC can cross the blood-brain barrier in humans. METHODS: Twelve patients with PD were given oral NAC twice daily for 2 days. Three doses were compared: 7 mg/kg, 35 mg/kg, and 70 mg/kg. NAC, cysteine, and glutathione were measured in the cerebrospinal fluid (CSF) at baseline and 90 min after the last dose. Cognitive and motor functions were assessed pre- and post-NAC administration using the Montreal Cognitive Assessment (MoCA) and the Unified Parkinson's Disease Rating Scale part III motor subscore (UPDRS-III). RESULTS: Oral NAC produced a dose-dependent increase in CSF NAC concentrations (p < 0.001), with the highest dose producing a CSF concentration of 9.26 ± 1.62 μM. There were no significant adverse events. NAC had no acute effect on motor or cognitive function. CONCLUSION: Orally administered NAC produces biologically relevant CSF NAC concentrations at doses that are well tolerated. The findings support the feasibility of NAC as a potential disease-modifying therapy for PD. Published by Elsevier Ltd.
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