title: Carboxyfullerene neuroprotection postinjury in Parkinsonian nonhuman primates.
abstract: OBJECTIVE
  We evaluated the efficacy of the potent antioxidant C3 to salvage nigrostriatal neuronal function after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exposure in nonhuman primates. C3 is a first-in-class functionalized water-soluble fullerene that reduces oxygen radical species associated with neurodegeneration in in vitro studies. However, C3 has 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. MPTP-lesioned 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-[(18) F]fluorodopa (FD; reflects dopa decarboxylase) and [(11) 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.
  
  
  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.
  
  
  CONCLUSIONS
  Systemic treatment with C3 reduced striatal injury and improved motor function despite administration after the MPTP injury process had begun. These data strongly support further development of C3 as a promising therapeutic agent for Parkinson disease.
authors.affiliation: Departments of Medicine, University of California, San Diego, San Diego, CA; Departments of Neurosciences, University of California, San Diego, San Diego, CA; Departments of Neurology, Washington University, St Louis, MO.
authors.forename: Laura L
authors.initials: LL
authors.lastname: Dugan
authors.forename: LinLin
authors.initials: L
authors.lastname: Tian
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Quick
authors.forename: Josh I
authors.initials: JI
authors.lastname: Hardt
authors.forename: Morvarid
authors.initials: M
authors.lastname: Karimi
authors.forename: Chris
authors.initials: C
authors.lastname: Brown
authors.forename: Susan
authors.initials: S
authors.lastname: Loftin
authors.forename: Hugh
authors.initials: H
authors.lastname: Flores
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Moerlein
authors.forename: John
authors.initials: J
authors.lastname: Polich
authors.forename: Samer D
authors.initials: SD
authors.lastname: Tabbal
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Mink
authors.forename: Joel S
authors.initials: JS
authors.lastname: Perlmutter
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002264:Carboxylic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004311:Double-Blind Method; D008252:Macaca fascicularis; D008297:Male; D017072:Neostriatum / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D010919:Placebos; D049268:Positron-Emission Tomography / Q000379:methods; D011897:Random Allocation; D013378:Substantia Nigra / Q000187:drug effects / Q000293:injuries / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D002264:Carboxylic Acids; D018696:Neuroprotective Agents; D010919:Placebos; C433784:carboxyfullerene C63(COOH)6; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine