N-Acetyl Cysteine May Support Dopamine Neurons in Parkinson\u27s Disease: Preliminary Clinical and Cell Line Data.

BACKGOUND: The purpose of this study was to assess the biological and clinical effects of n-acetyl-cysteine (NAC) in Parkinson\u27s disease (PD). METHODS: The overarching goal of this pilot study was to generate additional data about potentially protective properties of NAC in PD, using an in vitro and in vivo approach. In preparation for the clinical study we performed a cell tissue culture study with human embryonic stem cell (hESC)-derived midbrain dopamine (mDA) neurons that were treated with rotenone as a model for PD. The primary outcome in the cell tissue cultures was the number of cells that survived the insult with the neurotoxin rotenone. In the clinical study, patients continued their standard of care and were randomized to receive either daily NAC or were a waitlist control. Patients were evaluated before and after 3 months of receiving the NAC with DaTscan to measure dopamine transporter (DAT) binding and the Unified Parkinson\u27s Disease Rating Scale (UPDRS) to measure clinical symptoms. RESULTS: The cell line study showed that NAC exposure resulted in significantly more mDA neurons surviving after exposure to rotenone compared to no NAC, consistent with the protective effects of NAC previously observed. The clinical study showed significantly increased DAT binding in the caudate and putamen (mean increase ranging from 4.4% to 7.8%; p CONCLUSIONS: The results of this preliminary study demonstrate for the first time a potential direct effect of NAC on the dopamine system in PD patients, and this observation may be associated with positive clinical effects. A large-scale clinical trial to test the therapeutic efficacy of NAC in this population and to better elucidate the mechanism of action is warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT02445651

Demographics for the study subjects per group.

<p>Demographics for the study subjects per group.</p

Significant predictors of UPDRS Total Score.

<p>Significant predictors of UPDRS Total Score.</p

Mean pre-to-post-Tx differences in dopamine transporter binding.

<p>Mean pre-to-post-Tx differences in dopamine transporter binding.</p

N-Acetyl Cysteine May Support Dopamine Neurons in Parkinson's Disease: Preliminary Clinical and Cell Line Data - Fig 3

<p>Pre and post NAC DaTscans (left and right respectively) from one particularly responsive patient (A) shows a substantial increase in dopamine transporter binding in the basal ganglia (arrows). We also present (B) the paired t test results overlaid onto a standard MRI template using SPM8 software showing significantly greater binding (p<0.05) post NAC in the basal ganglia.</p

CONSORT Flow Diagram.

<p>CONSORT Flow Diagram.</p

Mean pre- and post-Tx UPDRS Total Score.

<p>Mean pre- and post-Tx UPDRS Total Score.</p

mDA neurons derived from hESCs were treated with N-acetyl cysteine at 10 μM for 3 days before challenge with rotenone (15nM and 30 nM) for 24 hours.

<p>TH+ neurons were quantified after cells were fixed and stained. Data was normalized as percentage of surviving mDA neurons compared to untreated control (100%). Treatment groups were compared with rotenone only groups using unpaired t-test. * p<0.05, ** p<0.01.</p