Grant: Operating Grant

Parkinson disease (PD) is a progressive neurological condition affecting 100,000 Canadians and will likely increase due to the aging population. The primary biochemical deficiency in PD is lack of the neurotransmitter dopamine, which is caused by loss of brain cells producing this neurotransmitter. There is no cure for PD. Preventing or protecting against brain dopamine cell death is not yet available for PD but laboratory studies have found promising agents. The most common medication used in PD, levodopa, is converted into dopamine in the brain. While this is an effective treatment, PD is a progressive disease and with time motor complications such as dyskinesias can develop. Dyskinesias are twisting and turning movements that may be quite disabling and can be very difficult to manage. Dr. Di Paolo has previously reported that DHA (omega-3) inhibits levodopa-induced dyskinesias in the MPTP monkey model of PD. Moreover DHA was reported to be neuroprotective against MPTP toxicity in mice. Dr. Wood has designed orally bioavailable plasmalogen precursor analogs that effectively increase steady-state DHA and lipoic acid levels in plasma. Lipoic acid also replenishes brain glutathione and thereby acts as a neuroprotectant. This project will determine if a plasmalogen treatment can reduce levodopa-induced dyskinesias in MPTP monkeys and will investigate the neuroprotective drug effects in MPTP mice. Brain dopamine, DHA and plasmalogens will be measured. This treatment could protect dopamine neurons from degeneration, delay progression of the disease as well as the use of levodopa and reduce clinical doses thus delaying the onset of dyskinesias. Moreover, if dyskinesias are already established the treatment may reduce their expression.