Do dopamine agonists or levodopa modify Parkinson's disease progression?
During the past decade, in vivo imaging of the nigrostriatal dopaminergic system has been developed as a research tool to monitor progressive dopaminergic neuron loss in Parkinson's disease (PD) and to assess the effect of medication on imaging outcomes. Recently two similar studies compared the effect of initial treatment with a dopamine agonist (pramipexole (CALM-PD CIT) or ropinirole (REAL-PET)) or levodopa on the progression of PD as measured by [123I]beta-CIT or [18F]Dopa imaging. These two clinical imaging studies targeting dopamine function with different imaging ligands and technology both demonstrate slowing in the rate of loss of [123I]beta-CIT or [18F]Dopa uptake in early PD patients treated with dopamine agonists compared with levodopa. The relative reduction in the per cent loss from baseline of [123I]beta-CIT uptake in the pramipexole versus the levodopa group was 47% at 22 months, 44% at 34 months and 37% at 46 months after initiating treatment. The relative reduction of 18F-dopa uptake in the ropinirole group versus the levodopa group was 35% at 24 months. These results should be very cautiously interpreted with regard to the effect of dopamine agonists or levodopa on clinical disease progression. These data highlight the need to compare imaging outcomes of dopamine neuronal loss with multiple meaningful clinical endpoints of disease progression in placebo controlled, larger and long-term studies.
Marek
K
K
The Institute for Neurodegenerative Disorders, New Haven, CT 06510, USA. kmarek@indd.org
Jennings
D
D
Seibyl
J
J
D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects / Q000627:therapeutic use*; D052160:Benzothiazoles; D002352:Carrier Proteins; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives*; D018450:Disease Progression; D018491:Dopamine Agonists / Q000627:therapeutic use*; D050483:Dopamine Plasma Membrane Transport Proteins; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D007457:Iodine Radioisotopes; D007980:Levodopa / Q000009:adverse effects / Q000627:therapeutic use*; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D017072:Neostriatum / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D009419:Nerve Tissue Proteins; D010300:Parkinson Disease / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D000077487:Pramipexole; D019275:Radiopharmaceuticals; D013844:Thiazoles / Q000627:therapeutic use; D014055:Tomography, Emission-Computed; D015899:Tomography, Emission-Computed, Single-Photon; D016896:Treatment Outcome; D014326:Tropanes
D000978:Antiparkinson Agents; D052160:Benzothiazoles; D002352:Carrier Proteins; D018491:Dopamine Agonists; D050483:Dopamine Plasma Membrane Transport Proteins; D007211:Indoles; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D019275:Radiopharmaceuticals; D013844:Thiazoles; D014326:Tropanes; C046649:ropinirole; C087552:2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane; C043437:fluorodopa F 18; D007980:Levodopa; D004295:Dihydroxyphenylalanine; D000077487:Pramipexole