Reducing Dyskinesia in Parkinson's Disease With Omega-3 Fatty Acids

Levodopa induced dyskinesias (LID) are involuntary, abnormal movements that occur in most
patients with Parkinson disease(PD) as a consequence of chronic use of the most effective
symptomatic drug, levodopa (LD). LID can range from subtle and unobtrusive to marked and
disabling. There are surprisingly few treatments for LID, including amantadine and deep brain
stimulation. In many instances, amantadine is either poorly tolerated, or provides inadequate
benefit, and only a small minority are appropriate candidates for surgery. Given the finding
that docosahexanoic acid (the most abundant omega-3 fatty acid in the brain), delays the
onset and reduces the severity of dyskinesia in two different animal models of LID, a trial
of docosahexanoic acid (DHA) in PD subjects about to start LD as part of their drug regimen,
to prevent or slow the progression of LID is warranted.

Prior to embarking on a large trial, preliminary data about safety and tolerability of DHA in
PD subjects is needed, and collection of this data is the primary outcome of this pilot
project proposal. 40 subjects who have not yet used levodopa, but are about to begin it will
be randomized to daily DHA or placebo. Safety laboratory testing, adverse event monitoring,
DHA plasma and CSF levels as well as compliance/subject retention will be outcomes collected.

In addition, preliminary data about modification of incidence rates will be collected and
compared between the two treatment groups. This information will aid in calculating an
appropriate sample size and treatment period for a larger definitive future study.

Dyskinesia manifests overwhelmingly when plasma levodopa levels are high enough to cause
anti-parkinsonian benefits, and lessens or stops when levodopa levels drop below a threshold.
Thus, the subject's dyskinesia measurements must occur during a levodopa administration
period. Dyskinesia measurement will occur during a two-hour levodopa cycle administered to
subjects at weeks 0, 6, 24, 52, 76. It is expected that a good proportion of subjects will
manifest dyskinesia within the two-year observation period, as previous studies using the
most objective means to measure dyskinesia report incidence rates of 67% or greater within
the first year of levodopa use. An instrument to measure dyskinesia developed by this center
will be used as an additional outcome, and is expected to measure dyskinesia more accurately
and with greater sensitivity than the gold standard methods of clinical rating scales.

By conclusion of this pilot project, the safety and tolerability, subject retention and
compliance, plasma/CSF levels of DHA administration will be determined. Trends in dyskinesia
development may be measured. This will provide the needed background information to proceed
with a future larger trial of DHA to prevent dyskinesia in PD.

Inclusion Criteria:

- Diagnosed with Parkinsons disease

- No levodopa (Sinemet) treatment or prior exposure to levodopa

Exclusion Criteria:

- Prior exposure to levodopa

- Unable to stand for 1 minute without aid

- Sensory deficits on feet

- Significant cognitive impairment

- Current use of dopamine receptor blocking medications (depakote, lithium, amiodarone,
tetrabenazine, metoclopramide, dronabinol)

- Current fish oil or lutein supplementation

- Allergy to soy