GPR109A and Parkinson's Disease: Role of Niacin in Outcome Measures

Inflammation plays a central role in Parkinson's disease. The use of anti-inflammatory drugs was found to reduce the risk of PD . Niacin may play an important role in reducing inflammation in PD. The investigators also found that individuals with PD have a chronic niacin deficiency .

The purposes of this study are to (1) examine the blood, urine and spinal fluid of persons with Parkinson's to look for evidence of inflammation and; (2) whether 6 months of vitamin B3 supplements may reduce the inflammation and/or improve symptoms.

Inflammation plays a central role in Parkinson's disease (PD) pathology \[1\] as evidenced by the presence of microglia in the substantia nigra in post-mortem samples \[2\] as well as activated microglia and cytokines in clinical and animal studies \[3\]. The use of non-aspirin non-steroidal anti-inflammatory drugs was found to reduce the risk of PD \[4\]. The investigators recently identified an anti-inflammatory receptor GPR109A that is upregulated in PD \[5\]. Niacin has a high affinity for this receptor, suggesting that it (niacin) may play an important role in reducing inflammation in PD. The investigators also found that individuals with PD have a chronic niacin deficiency \[5\]. Using seed funding from the local PD chapter, the investigators obtained pilot data which suggested that restoring the deficiency via over-the-counter (OTC) supplementation reduced inflammation and decreased the severity of the disease symptoms \[6\]. In this VA-funded study, the investigators will determine the effect of 6 months' OTC niacin supplementation on inflammation (as assessed in the blood and spinal fluid) and severity of the PD symptoms.

Eligibility Criteria:
Inclusion Criteria:

* PD subjects will be adult men and women diagnosed with idiopathic mild to moderately severe PD defined as modified Hoehn \& Yahr Stages I-III (while "On").

  * PD is defined according to the United Kingdom Brain Bank Criteria made at least six months prior to recruitment to the study.
  * PD features include the presence of at least two of the four cardinal clinical manifestations of the disease, which are tremor, rigidity, bradykinesia, and disturbances of posture or gait, without any other known or suspected cause of Parkinsonism.
* Subjects should be stabilized on PD medication for at least 3 months before enrollment into the study.
* Subjects' PD drug prescriptions will not be altered nor withheld during the study, i.e., they will be tested while "On."
* The patient will have signed informed consent.
* Subjects who do not have PD (i.e., healthy or have other medical conditions such as traumatic brain injury (TBI), stroke, or other syndromes in which inflammation plays a role in the condition) will also be recruited as control subjects.
* This will allow us to estimate whether these other conditions show similar or unique inflammatory profile.

Exclusion Criteria:

* Subjects will be excluded if they had previous brain surgery or other severe neurological problems

  * intracerebral hemorrhage
  * traumatic brain injury
  * central nervous system malignancy
  * active central nervous system (CNS) infection
  * significant stroke
  * Alzheimer disease or any type of implanted stimulator including but not limited to Deep Brain Stimulator (DBS) or pacemaker
* All subjects must be without evidence of dementia, defined as a score \> 24 the Mini-Mental State Examination and able to understand test instructions
* Subjects must not have functional blindness (inability to participate in gait and visuomotor assessments) or lower limb amputation higher than the forefoot or any orthopedic problem that precludes performance of physical tests
* Allergic to niacin
* Significant cardiac, pulmonary, hepatic, gastrointestinal, or renal disease

  * e.g., New York Heart Association Class III or IV congestive heart failure
  * endocarditis
  * pulmonary insufficiency symptomatic at rest or with mild physical exertion
  * acute or chronic hepatitis
  * renal failure requiring dialysis
  * second and third degree atrioventricular block or sick sinus syndrome), or diabetes are also exclusionary factors