Dopamine Replacement Therapy and Parkinson's Disease
EMSL Project ID
41090
Abstract
Dopamine (DA) replacement therapy with L-3,4-dihydroxyphenylalanine (L-DOPA) is currently the most efficient pharmacotherapy for patients with Parkinson's disease (PD), but with disease progression and long-term L-DOPA treatment complications occur in the majority of patients. The main side effects are troublesome motor complications such as wearing off- fluctuations and peak-dose dyskinesia, i.e. abnormal involuntary movements. In patients, the occurrence of L-DOPA induced dyskinesia (LID) has been linked to, for example; a) disease duration, b) L-DOPA treatment duration, c) a higher initial dose of L-DOPA, d) a higher total dose L-DOPA, and e) to late onset of DA agonist adjunctive therapy. Once LID is established it is very difficult to counteract and today's treatment management is aimed at delaying the development of LID. Replacement of L-DOPA with other DA agonists in the initial treatment of PD has been one successful strategy that delays on-set of LID, but with disease progression L-DOPA is still required for satisfactory symptomatic relief and thus an increase risk of developing LID.
Previous studies, detailed later in this proposal, imply that although the extent and pattern of DA-denervation may not cause individual susceptibility to develop LID, the loss of striatal dopamine may induce important changes of function of the striatal medium-sized spiny neurons that may predetermine LID severity.
We propose a study of the effects of DA-denervation followed by L-DOPA treatment on the levels of neuropeptides and proteins of the striatum of rats with LID using a method of detection of many different molecular species at the same time, which is why we propose that Matrix Assisted Laser Desorption Ionization (MALDI) Imaging Mass Spectrometry (IMS) in combination with The PNNL-developed Accurate Mass and Time (AMT) Tag approach is the ideal method for this project.
Project Details
Project type
Exploratory Research
Start Date
2011-02-08
End Date
2012-02-12
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members