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

Abstract

BackgoundThe purpose of this study was to assess the biological and clinical effects of n-acetyl-cysteine (NAC) in Parkinson’s disease (PD).MethodsThe 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’s Disease Rating Scale (UPDRS) to measure clinical symptoms.ResultsThe 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<0.05 for all values) in the PD group treated with NAC, and no measurable changes in the control group. UPDRS scores were also significantly improved in the NAC group (mean improvement of 12.9%, p = 0.01).ConclusionsThe 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 RegistrationClinicalTrials.gov NCT02445651

Repeated‐Dose Oral N‐Acetylcysteine in Parkinson's Disease: Pharmacokinetics and Effect on Brain Glutathione and Oxidative Stress

“…These side effects were mild to moderate and reversible, resolving within a few days or weeks of stopping NAC. It is possible that the adverse events are dose dependent, as investigators using a lower dose (1200 mg NAC/day) did not observe worsening of parkinsonian symptoms, but instead patients who took 1200 mg/day in combination with weekly intravenous dosing reported symptomatic improvement . A major difference between our study and that conducted by Monti et al was that the latter study used weekly intravenous doses in combination with relatively low oral daily doses.…”

“…Long‐term oral administration of NAC in a PD mouse model substantially reduced neuronal loss, oxidative stress, and motor abnormalities . Recently, a combination intravenous/oral NAC therapy was reported to decrease symptoms in individuals with PD …”

Phase IIb Study of Intranasal Glutathione in Parkinson’s Disease

“…A recent publication has demonstrated that the glutathione precursor, NAC, produced a mean 13% improvement in UPDRS scores, and significantly increased DAT density in the caudate and putamen in PD, suggesting that NAC and/or GSH can affect dopaminergic neurotransmission [28]. In addition to having potential as a disease-modifying agent, these data support the idea that (in)GSH may also have symptomatic efficacy.…”

N‐Acetyl Cysteine Is Associated With Dopaminergic Improvement in Parkinson's Disease

“…We previously reported findings from cell line data and preliminary clinical effects of N‐acetyl‐cysteine (NAC), which suggested possible improvements in dopamine transporter (DAT) binding in a small number of patients with PD who received NAC, using ioflupane DaTscan single photon emission computed tomography (SPECT) imaging . Three months of NAC treatment resulted in increased DAT binding in the basal ganglia; hence, the present study extends those results with a more robust study number and comprehensive analyses.…”

“…In the pilot study mentioned above, we used ioflupane DaTscan SPECT imaging and the Unified Parkinson's Disease Rating Scale (UPDRS) scores to assess whether there was any positive signal from the NAC treatment. The primary goals of the present study were to provide expanded data regarding the effect of NAC administration on DAT binding and symptoms in patients with PD.…”