Carboxyfullerene neuroprotection postinjury in Parkinsonian nonhuman primates. Issue 3 (22nd July 2014)

• Record Type: Journal Article
• Authors: Dugan, Laura L.; Tian, LinLin; Quick, Kevin L.; Hardt, Josh I.; Karimi, Morvarid; Brown, Chris; Loftin, Susan; Flores, Hugh; Moerlein, Stephen M.; Polich, John; Tabbal, Samer D.; Mink, Jonathan W.; Perlmutter, Joel S.
• Is Part Of: Annals of neurology. Volume 76:Issue 3(2014:Sep.)
• Page Start: 393
• Page End: 402
• Publication Date: 2014-07-22
• Subjects: Neurology -- Periodicals; Pediatric neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; 616.8
• DOI: 10.1002/ana.24220
• Languages: English
• ISSNs: 0364-5134

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ana24220-sec-0001" sec-type="section"> <title>Objective</title> <p>We evaluated the efficacy of the potent antioxidant C<sub>3</sub> to salvage nigrostriatal neuronal function after 1‐methyl‐4‐phenyl‐1, 2, 3, 6‐tetrahydropyridine (MPTP) exposure in nonhuman primates. C<sub>3</sub> is a first‐in‐class functionalized water‐soluble fullerene that reduces oxygen radical species associated with neurodegeneration in in vitro studies. However, C<sub>3</sub> has not been evaluated as a neuroprotective agent in a Parkinson model in vivo.</p> </sec> <sec id="ana24220-sec-0002" sec-type="section"> <title>Methods</title> <p> <italic>Macaque fascicularis</italic> monkeys were used in a double‐blind, placebo‐controlled study design. MPTP‐lesioned primates were given systemic C<sub>3</sub> (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‐[<sup>18</sup>F]fluorodopa (FD; reflects dopa decarboxylase) and [<sup>11</sup>C]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.</p> </sec> <sec id="ana24220-sec-0003" sec-type="section"> <title>Results</title> <p>After 2 months, C<sub>3</sub>‐treated monkeys had significantly improved parkinsonian motor ratings, greater striatal FD and DTBZ uptake, and higher striatal dopamine levels. None of the C<sub>3</sub>‐treated animals developed any toxicity.</p> </sec> <sec id="ana24220-sec-0004" sec-type="section"> <title>Interpretation</title> <p>Systemic treatment with C<sub>3</sub> reduced striatal injury and improved motor function despite administration after the MPTP injury process had begun. These data strongly support further development of C<sub>3</sub> as a promising therapeutic agent for Parkinson disease. Ann Neurol 2014;76:393–402</p> </sec> </abstract>