The Stanford Parkinson's Disease Plasma Study

Parkinson's disease (PD) is a neurodegenerative disease that affects over 1.6 million people
in the United States and whose incidence increases with age, affecting over 1% of people over
the age of 65. The neuropathological processes involved in PD are widespread throughout the
brain, and are reflected in a constellation of motor, cognitive, mood and other non-motor
symptoms. Treatments to date have largely focused on dopamine replacement strategies or deep
brain stimulation, both symptomatic treatments.

As neurodegenerative diseases progress, there are major changes throughout the body and
brain. These changes are transmitted in the body via the circulatory system between organs,
tissues and cells. Recent findings from multiple laboratories have shown that infusions of
young plasma into aging rodents can have beneficial effects on cognitive functions. This
suggests that the circulating components of plasma can improve cognitive and disease-relevant
symptoms. This has motivated the field to treat multiple disorders with blood products and
their constituent active components.

The established safety of blood transfusions allows the investigators to test whether
infusions of young plasma can ease the neurological symptoms in human subjects with
neurodegenerative diseases. A study that is ongoing at Stanford, in the department of
Neurology and Neurological Sciences, is testing whether infusions of young plasma can
ameliorate the cognitive impairment in patients with Alzheimer's disease (ClinicalTrials.gov
identifier NCT02256306). To date, this has been well-tolerated by the participants, without
major adverse effects.

The investigator proposes to test the safety and efficacy of transfusing young plasma into PD
participants, in order to establish its effects on motor and cognitive functions in
participants in a Phase 1 study. The successful completion of this study will inform the
design of future, larger and multicenter studies with the goal to determine whether infusions
of young plasma can ameliorate the neurodegenerative symptoms and underlying pathophysiology
in Parkinson's disease.

Inclusion Criteria:

- A diagnosis of clinically probable or established Parkinson's Disease (MDS criteria)

- Subject must be on a stable dose of dopaminergic medication and/or Deep Brain
Stimulation (DBS) parameters for at least 4 weeks prior to screening and for the
duration of the study

- Subject must be competent to sign consent

- Subject must be willing to commit to being available for testing and infusions for 6
consecutive weeks (2 testing consecutive weeks, 4 infusion consecutive weeks) followed
by two visits a month after final infusion.

- The availability of a study partner who knows the patient well and is willing to
accompany the subject to all trial (optional if participant is able to consent and
travel by self)

Exclusion Criteria:

- The participation in any other interventional clinical trial

- The inability to travel to Stanford

- Inability to walk without assistance in the off or on medication state

- The clinically determined presence of dementia

- A clinical suspicion/diagnosis of Multiple System Atrophy (MSA), Progressive
Supranuclear Palsy (PSP), Lewy Body Dementia (LBD), Essential Tremor (ET)

- Subject's pregnancy or likelihood of pregnancy within the next 6 months.

- Subject's positive test results for Hepatitis B, Hepatitis C or HIV at screening

- Any other condition or situation that the investigator believes may interfere with the
safety of the subject or the intent and conduct of the study

- Subject's medical history of:

Stroke Anaphylaxis Gout- may cause an increase in uric acid Prior adverse reaction to any
human blood product Any history of a blood coagulation disorder or hypercoagulability
Congestive heart failure Uncontrolled hypertension Renal failure Prior intolerance to
intravenous fluids Recent history of uncontrolled atrial fibrillation immunoglobulin A
deficiency (by history)

- Subject's relation to medications or other treatments:

- Any concurrent use of an anticoagulant therapy. Antiplatelet drugs (e.g., aspirin or
clopidogrel) are acceptable.

- The use of Inosine, which may alter urate levels

- Initiation or change in the dosage of a cholinesterase inhibitor or memantine during
the trial. A participant already on a cholinesterase inhibitor or memantine must be on
a stable dose for at least one month prior to Screening.

- Concurrent participation in another interventional treatment trial for Parkinson's
disease. If there was prior participation, the last dose of the investigational agent
must have been at least 6 months prior to Screening.

- Treatment with any human blood product, including intravenous immunoglobulin, during
the 6 months prior to Screening or during the trial.

- Concurrent daily treatment with benzodiazepines, typical or atypical antipsychotics,
long-acting opioids, or other medications that, in the investigator's opinion,
interfere with cognition. Intermittent treatment with short-acting benzodiazepines or
atypical antipsychotics may be permitted, provided that no dose is administered within
the 72 hours preceding any cognitive assessment.