• GSH levels in brain and peripheral circulation in all subjects post-NAC administration [ Designated as safety issue: No ]
  

Drug: N-acetylcysteine
Single, intravenous administration of N-acetylcysteine 150 mg/kg
Other Name: NAC

Oxidative stress is implicated in the pathogenesis of a number of lysosomal and neurodegenerative diseases such as Gaucher's disease (GD) and Parkinson's disease (PD), respectively. Further, levels of glutathione (GSH), a prevalent endogenous antioxidant, are decreased in the postmortem substantia nigra (SN) of individuals with PD, indicating increased oxidative stress, although this has yet not been confirmed in vivo. Increases in intracellular oxidative stress have also been observed in primary fibroblast cultures obtained from patients with GD, where enzyme replacement therapy resulted in increases in total GSH. The hypothesis that oxidative stress plays a key role in the neurodegeneration associated with PD and GD suggests that antioxidants may be useful in altering disease progression.

N-acetylcysteine (NAC) is a well-known antioxidant that is thought to act both as a free radical scavenger and as a cysteine donor for the synthesis of GSH. NAC may be beneficial in the treatment of GD and PD. Magnetic resonance spectroscopy (MRS) methods may be able to determine if there are effects from NAC on central nervous system GSH levels. In addition, use of red blood cell (RBC) measurements of GSH, if correlated with brain concentrations, could serve as an easily measured biomarker to help characterize and monitor response to therapy. The investigators therefore propose to conduct a study of the effect of a single, intravenously (i.v.) administered dose of NAC on central (brain) measures of GSH and peripheral (RBC) measures of GSH in people with PD, GD and healthy controls, through the use of simultaneous MRS techniques and pharmacokinetic studies. The investigators hypothesis and specific aims are as follows:

Hypothesis: RBC and brain GSH concentrations will increase following i.v. NAC infusions in individuals with Parkinson's disease (PD), Gaucher's disease (GD) and control participants.

Specific Aims:

1. Quantitate baseline plasma and red blood cell GSH concentrations in those with PD, GD and controls; and characterize NAC and GSH pharmacokinetics after a single i.v. NAC infusion.
2. Quantitate brain GSH levels (as ascertained through MRS) in those with PD, GD and controls at baseline and after a single i.v. NAC infusion simultaneously with Aim 1.
3. Construct a pharmacokinetic model to evaluate the relationship between peripheral (plasma and RBC) and central (brain) GSH measurements.