Does N-Acetylcysteine Decrease Spontaneous Oxidation of Central Neural Dopamine in Parkinson's Disease?
Does N-Acetylcysteine Decrease Spontaneous Oxidation of Central Neural Dopamine in Parkinson's Disease?
Background:

 Parkinson s disease (PD) causes slow movement, stiffness, and poor balance. Many symptoms are
 due to the loss of brain cells that make the brain chemical dopamine. The cells may be
 damaged by the breakdown of dopamine by a process called oxidation. The drug N-acetylcysteine
 (NAC) can act as an antioxidant. Researchers want to test if NAC can decrease the oxidation
 of brain dopamine in people with PD.

 Objective:

 To look at the effect of NAC on brain chemistry in people with PD.

 Eligibility:

 People ages 18 and older with PD that was diagnosed within the past 5 years. They must be
 taking a monoamine oxidase inhibitor.

 Design:

 Participants will be screened with:

 Medical history

 Physical exam

 Blood and urine tests

 Participants will be hospitalized for 4 to 8 days.

 On day 1, they will have blood and urine tests. They cannot eat or drink anything but water
 and their medications for several hours. Late in the morning they will have a meal.

 About 2 hours later they will have a spinal tap. For this, a numbing medicine is injected
 into the back. A needle is inserted between the bones in the back to remove a small amount of
 fluid. The spinal tap may be use x-rays to see inside the body.

 After the spinal tap, they will start taking NAC by mouth.

 They will take NAC twice a day for 2 more days.

 On the next day, they will not eat until a meal in the late morning. They will take a final
 NAC dose.

 About 2 hours later they will have a second spinal tap.
Objective:

 This study is to test whether N-acetylcysteine (NAC) inhibits the spontaneous oxidation of
 central neural dopamine as indicated by the cerebrospinal fluid (CSF) concentration of
 5-S-cysteinyl-dopamine (Cys-DA) in patients with Parkinson s disease (PD).

 Study population:

 The study population comprises up to 35 patients with early (less than or equal to 5 years
 from diagnosis), mild, levodopa-untreated PD. The patients will be on an inhibitor of
 monoamine oxidase (MAO) that is prescribed for their disease.

 Design:

 The study has a one group, pretest-posttest design. Each patient undergoes a lumbar puncture
 (LP) as an inpatient at the NIH Clinical Center to obtain cerebrospinal fluid (CSF) for
 assays of Cys-DA, 3,4-dihydroxyphenylacetic acid (DOPAC), and related biochemicals. The
 second LP is done after the patient has taken at least 5 doses of NAC (2 grams orally twice
 per day). The LP takes place about 2 hours after the last NAC dose.

 Outcome measures:

 The main outcome measure is the CSF concentration of Cys-DA. Other outcome measures are
 levels of other catecholamine-related neurochemicals or of indices of oxidative stress.
 Depending on the results, an exploratory study may be done involving NAC at 1 gram orally
 twice per day.
-  INCLUSION CRITERIA:

 -  PD diagnosed within the past 5 years

 -  Taking a monoamine oxidase (MAO) inhibitor

 -  Able to provide consent

 -  At least18 years old

 EXCLUSION CRITERIA:

 -  Taking levodopa in any form

 -  Known allergy to NAC

 -  Already taking an anti-oxidant dietary supplement (e.g., Olive Leaf Extract, MitoQ)

 -  A condition that would increase risk from a lumbar puncture (e.g., symptomatic spinal
 stenosis or myoclonus)

 -  History of a post-spinal headache that required treatment with a blood patch

 -  On a prescribed anti-coagulant (e.g., Coumadin, Plavix)

 -  Pregnant or breast-feeding

 -  History of alcohol or drug abuse

 -  Any medical condition thatcould put subjects at increased risk. Potential participants
 are excluded who have evidence of bone marrow, liver, or kidney failure based on
 abnormal screening lab results.

 -  On a medication that could interfere with the scientific results. An example of an
 exclusionary drug is the catechol-O-methyltransferase inhibitor entacapone. Tricyclic
 anti-depressants are another type of exclusionary drug