The overall goal of this study will be to further our understanding of how N Acetyl Cysteine (NAC) can help to support dopaminergic function in patients with Parkinson's disease (PD). We plan to use pre and post Positron emission tomography magnetic resonance imaging (PET-MRI) with [F-18] Fluorodopa (FDOPA) to measure dopamine function, and neurological measures to assess clinical symptoms, in patients with PD who are given oral capsules plus IV infusions of NAC in addition to standard of care for PD for 6 ±3 months in an open label cross over design. Serum measures of NAC concentrations, magnetic resonance spectroscopy (MRS) to measure inflammatory and oxidative stress markers, may be conducted.

The study consists of two arms in this crossover design study. The first arm of this study will receive intravenous and oral NAC, which is a strong antioxidant that increases brain glutathione, which may be beneficial in PD. NAC, is the N-acetyl derivative of the naturally occurring amino acid, L-cysteine. It is a common over-the-counter supplement and also is available as an injectable pharmaceutical that protects the liver in cases of acetaminophen overdose. Laboratory studies have displayed some benefits to use of NAC, such as its potential to counteract intracellular damage that leads to dopaminergic neuron death. It also has the potential to reduce markers of oxidative damage, protect against dopamine cell death from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity, and to increase glutathione in blood, which might be useful in preventing oxidative damage in PD patients. The second arm will be a waitlist control receiving standard PD care. It should be noted that both arms will receive standard of care treatment for PD which will be augmented with NAC. A key component of this study is to evaluate the effects of NAC on dopamine, using PET imaging with FDOPA. Specifically, we will plan to study changes in dopamine levels before and after receiving approximately nutritional support with NAC.. This will allow us to evaluate whether NAC helps to support dopamine function. FDOPA PET imaging will be conducted at baseline and then after the nutritional support or standard of care for the waitlist arm. Then the waitlist group will receive NAC and the arm that received NAC initially will be crossed over to a standard of care group. FDOPA imaging will be conducted at the end of that period.

For evaluation of the dopamine function, [F-18] Fluorodopa (FDOPA), dose (5-10 millicurie (mCi), ± 20%) will be injected intravenously into an antecubital vein. Subjects will be premedicated with 200 mg of carbidopa orally approximately one hour prior to injection.

FDOPA has been available for over 30 years but has not been previously approved for commercial use by the FDA.We will be obtaining the FDOPA from the University of Pennsylvania cyclotron that has produced FDOPA for many Investigational New Drug applications (INDs) It will also be beneficial to assess whether there are specific changes in levels of different molecules that are related to energy consumption and oxidative stress. Proton MR spectroscopy (1H-MRS) has been previously performed in Parkinson's disease (PD) and parkinsonian syndromes to evaluate in vivo concentrations of basal ganglia and cerebral cortex metabolites such as N-acetylaspartate (NAA), choline (Cho), and creatine (Cr). We plan to include MRS as an additional biomarker to evaluate the potential effects of the nutritional supplements and/or NAC on oxidative stress and cerebral activity in PD patients.

Inclusion Criteria:

1. Clinical diagnosis of PD
2. Age 30 years old and older
3. Physically independent, ambulatory
4. Hoehn and Yahr score of I-III inclusive.
5. On stable antiparkinsonian medication for at least one month
6. Women of childbearing potential will confirm a negative pregnancy test and must practice effective contraception during the period of pilot study. In addition, male subjects who have a partner of childbearing age should practice effective contraception.

Exclusion Criteria:

1. Known allergy to NAC
2. Previous brain surgery.
3. Cognitive impairment by evaluation or known score on Mini-Mental Status examination of 25 or lower.
4. Wheelchair-bound or bed-ridden, non-ambulatory.
5. Intracranial abnormalities that may complicate interpretation of the brain scans (e.g., stroke, tumor, vascular abnormality affecting the target area).
6. History of head trauma with loss of consciousness > 48 hours.
7. Any medical disorder or physical condition that could reasonably be expected to interfere with the assessment of parkinsonian syndrome symptoms, or with any of the study assessments including the PET-MRI imaging.
8. Metal in the body that would prevent MRI scanning (as determined by the PI)
9. Patients with evidence of a significant psychiatric disorder by history/examination that would prevent completion of the study will not be allowed to participate.
10. Patients with current alcohol or drug abuse
11. Pregnant or lactating women.
12. Enrollment in active clinical trial/ experimental therapy within the prior 30 days.
13. Pending surgery during the course of the study.
14. History of thrombocytopenia or clotting disorders.
15. Cancer patients receiving active chemotherapy.
16. Severe gastroesophageal reflux disease.
17. History of uncontrolled diabetes, , gastroesophageal reflux disease, thyroid conditions
18. History of uncontrolled asthma.
19. History of severe kidney disease (if a patient reports this problem, a serum creatinine will be checked to assess glomerular filtration rate (GFR) and if it is less than 30, they will be excluded),
20. Patients taking medications that might interact with NAC involved in this study will be evaluated on a case-by-case basis by the PI or study physician. These medications include: Medications for high blood pressure; Medications that slow blood clotting; Medications for diabetes; Nitroglycerin.

After each participant completes the study, study scan data will be shared with co-investigators; participants may receive a copy of each scan after study completion.

Study scan report will be offered to the subject after subject completes study

Access only to authorized research staff and study participants