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Imaging Marker Detects Parkinson's Degeneration

An imaging marker of dopamine neuronal loss detects treatment-related changes in the progressive loss of striatal dopamine transporters in patients with early Parkinson's disease.

This marker, [123I] -CIT (2 -carboxymethoxty-3 {4-iodophenyl}tropane), uses single-photon emission computed tomography (SPECT).

This imaging data highlight the need for further comparison of the imaging marker with clinical end points of Parkinson's progression to assess fully its clinical relevance through long-term studies, suggest North American Parkinson Study Group investigators.

"In vivo dopamine transporter imaging with [123I] beta-SPECT demonstrated reduced loss of striatal [123I] beta-CIT uptake in patients with Parkinson's treated initially with pramipexole, compared with levodopa," they explain.

"As [123I] beta-CIT SPECT is a quantitative biomarker for striatal dopamine neuron terminals, these data indicate that treatment with pramipexole, levodopa or both may modify the dopaminergic neuronal degeneration of Parkinson's."

The researchers evaluated 82 patients with early Parkinson's over 46 months. All patients were recruited at 17 clinical sites in the United States and Canada between November 1996 and August 1997. The participants required dopaminergic therapy because of emerging disability. Forty-two patients were randomised to receive pramipexole with levodopa placebo while the other 40 patients were received carbidopa/levodopa with pramipexole placebo.

Dosage was escalated for patients with residual disability during the first 10 weeks; open-label levodopa could be added subsequently. Dosage could be modified further after 24 months of follow-up.

Sequential SPECT imaging showed a decline in mean [123I] -CIT striatal uptake of approximately 5.2 percent per year. The mean loss in striatal [123I] beta-CIT uptake from baseline was reduced significantly in members of the pramipexole group compared with the levodopa group, over 46 months.

The researchers say identification of disease-modifying therapies for Parkinson's is a major unmet need and they note that studies evaluating neuro-protective medication effects have been limited by the lack of a clear endpoint defining neuro-protection. This has been confounded by potential simultaneous symptomatic and neuro-protective benefits.

"In vivo imaging offers the potential of an objective method to monitor neuronal degeneration unaffected by a short-term symptomatic drug effect," they suggest.
JAMA, 2002; 287: 1653-1661. "Dopamine Transporter Brain Imaging to Assess the Effects of Pramipexole vs Levodopa on Parkinson Disease Progression"

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