Cerebrospinal fluid concentrations of N-acetylcysteine after oral administration in Parkinson's disease

• Published in: Parkinsonism & related disorders Vol. 21; no. 5; pp. 500 - 503
• Main Authors: Katz, Maya, Won, Seok Joon, Park, Youngja, Orr, Adrienne, Jones, Dean P, Swanson, Raymond A, Glass, Graham A
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.05.2015
• Subjects: Acetylcysteine - administration & dosage; Acetylcysteine - cerebrospinal fluid; Administration, Oral; Aged; Aged, 80 and over; Biomarkers - cerebrospinal fluid; Blood-Brain Barrier - drug effects; Blood-Brain Barrier - metabolism; Cysteine; Dose-Response Relationship, Drug; Female; Glutathione; Humans; Male; Middle Aged; Neurology; Neuroprotection; Parkinson Disease - cerebrospinal fluid; Parkinson Disease - drug therapy; Parkinson's disease; Therapeutics; Neuroprotection; Cysteine; Parkinson's disease; Therapeutics; Glutathione
• ISSN: 1353-8020; 1873-5126
• DOI: 10.1016/j.parkreldis.2015.02.020

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.