Rotigotine treatment partially protects from MPTP toxicity in a progressive macaque model of Parkinson’s disease.
Experimental Neurology. 2007-02-01; 203(2): 415-422
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1. Exp Neurol. 2007 Feb;203(2):415-22. Epub 2006 Oct 12.
Rotigotine treatment partially protects from MPTP toxicity in a progressive
macaque model of Parkinson’s disease.
Scheller D(1), Chan P, Li Q, Wu T, Zhang R, Guan L, Ravenscroft P, Guigoni C,
Crossman AR, Hill M, Bezard E.
(1)SCHWARZ BIOSCIENCES GmbH, Alfred-Nobel Strasse 10, Monheim, Germany.
Clinical DA agonist monotherapy trials, which used in vivo imaging of the DA
transporter (DAT) to assess the rate of progression of nigrostriatal
degeneration, have failed to demonstrate consistent evidence for neuroprotection.
The present study aims at reconciling these experimental and clinical data by
testing the protective property of the continuously delivered D3/D2/D1 dopamine
receptor agonist rotigotine. Using a progressive
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned (MPTP) macaque model that
mimics the progression of Parkinson’s disease in vivo ([99mTc]-TRODAT-1 single
photon emission computed tomography (SPECT)) and ex vivo ([125I]-nortropane DAT
labelling) endpoints were evaluated. After 38 days of treatment followed by two
weeks of washout, rotigotine-treated animals were significantly less parkinsonian
than the vehicle-treated ones. Such behavioural difference is the consequence of
a partial protection of the DA terminals as could be confirmed by ex vivo DAT
labelling. However, the protection of nerve terminals was not detected using
SPECT. The data suggest that rotigotine exerts partial protection but that
conventional imaging would not be able to identify such protection.
PMID: 17045989 [Indexed for MEDLINE]