Carboxyfullerene neuroprotection postinjury in parkinsonian nonhuman primates

Laura L. Dugan, Lin Lin Tian, Kevin L. Quick, Josh I. Hardt, Morvarid Karimi, Chris Brown, Susan Loftin, Hugh Flores, Stephen M. Moerlein, John Polich, Samer D. Tabbal, Jonathan W. Mink, Joel S. Perlmutter

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Objective: We evaluated the efficacy of the potent antioxidant C3to salvage nigrostriatal neuronal function after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exposure in nonhuman primates. C3is a first-in-class functionalized water-soluble fullerene that reduces oxygen radical species associated with neurodegeneration in in vitro studies. However, C3has not been evaluated as a neuroprotective agent in a Parkinson model in vivo. Methods: Macaque fascicularis monkeys were used in a double-blind, placebo-controlled study design. MPTPlesioned primates were given systemic C3(n = 8) or placebo (n = 7) for 2 months starting 1 week after MPTP. Outcomes included in vivo behavioral measures of motor parkinsonism using a validated nonhuman primate rating scale, kinematic analyses of peak upper extremity velocity, positron emission tomography imaging of 6-[18F]fluorodopa (FD; reflects dopa decarboxylase) and [11C]dihydrotetrabenazine (DTBZ; reflects vesicular monoamine transporter type 2), ex vivo quantification of striatal dopamine, and stereologic counts of tyrosine hydroxylase-immunostained neurons in substantia nigra. Results: After 2 months, C3-treated monkeys had significantly improved parkinsonian motor ratings, greater striatal FD and DTBZ uptake, and higher striatal dopamine levels. None of the C3-treated animals developed any toxicity. Interpretation: Systemic treatment with C3reduced striatal injury and improved motor function despite administration after the MPTP injury process had begun. These data strongly support further development of C3as a promising therapeutic agent for Parkinson disease.

Original languageEnglish (US)
Pages (from-to)393-402
Number of pages10
JournalAnnals of Neurology
Volume76
Issue number3
DOIs
StatePublished - Sep 1 2014

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

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