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


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: 7mg/kg, 35mg/kg, and 70mg/kg. NAC, cysteine, and glutathione were measured in the cerebrospinal fluid (CSF) at baseline and 90min 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±1.62μM. 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.

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