Characterizing Biomarkers of Early Parkinson's Disease Progression (TREG)

Objectives:

Parkinson's disease is the second most common neurodegenerative condition worldwide, and
while both motor and non-motor symptoms can be improved with symptomatic therapies, there are
currently no drugs that slow or halt progression of the disease. All previous trials of
neuroprotective therapies have failed, in large part due to the lack of objective, sensitive
biomarkers of Parkinson's disease progression.

Plan:

The proposed study aims to characterize the rate of change in a peripheral blood marker of
inflammation (Treg percentage) and three quantitative motor measures (finger tapping, 9-hole
peg test and peak turn velocity) in a cohort of 25 untreated PD patients with motor testing
and blood sampling performed at baseline and at 6 months

Methods:

Participants will have three visits to the Portland VA over a 12 month period. Assessments
will be made regarding their Parkinson's disease progression (motor ability and gait and
balance). At each visit, a VA phlebotomist will draw whole blood. The VA lab will analyze
whole blood for metabolic CBC with differential. The research team will hand carry blood
samples from the VA phlebotomist to Dr. Quinn's VA lab in BLDG 103 - E143. A plasma sample
will be added to the Neurologic Disorders Repository (MIRB # 3129). Peripheral blood
mononuclear cells (PBMC) will be isolated from buffy coats using Ficoll-Paque. The PBMC will
be frozen and batch analyzed for T lymphocytes using flow cytometry at OHSU.

Inclusion Criteria:

- Men and women between the ages of 40 and 80 years

- Diagnosis of idiopathic Parkinson's disease based on the UK PD Brain Bank criteria35

- PD diagnosis within 5 years (≤ 5 years)

- Hoehn and Yahr severity stage less than or equal to 3 (Mild to moderate bilateral
disease; some postural instability; physically independent).36

- Remain untreated with levodopa or a dopamine agonist for the duration of the study (up
to 7 months, can have treatment with MAO-B inhibitors rasagiline or selegiline)

- Able to understand and give informed consent for the study

- Able to stand and walk unassisted

Exclusion Criteria:

- Current use of dopamine-blocking therapy or significant history of dopamine-blocking
therapy (> 1 yr of daily use of the following: typical and atypical antipsychotics
except for quetiapine and clozapine, metoclopramide, prochlorperazine, tetrabenazine,
reserpine)

- Autoimmune disease or current anti-inflammatory or immunomodulatory therapy (aspirin,
Tylenol, ibuprofen, naproxen OK)

- Other condition already causing gait dysfunction or likely to cause significant change
in motor/gait function over 6 month period (i.e. knee or hip replacement within the
past 6 months or surgery planned during the study, peripheral neuropathy causing
impaired proprioception at big toes)

- History of treatment with carbidopa/levodopa, dopamine agonist, or amantadine (can
have history of treatment with MAO-B inhibitors rasagiline or selegiline)

- Patient anticipates that they will require symptomatic treatment for PD within the
next 6 months