Carboxyfullerene neuroprotection postinjury in Parkinsonian nonhuman primates

Ann Neurol. 2014 Sep;76(3):393-402. doi: 10.1002/ana.24220. Epub 2014 Jul 22.


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.

Interpretation: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / pharmacology
  • Animals
  • Behavior, Animal / drug effects*
  • Carboxylic Acids / administration & dosage
  • Carboxylic Acids / pharmacology*
  • Disease Models, Animal
  • Dopamine / metabolism
  • Double-Blind Method
  • Macaca fascicularis
  • Male
  • Neostriatum / drug effects*
  • Neostriatum / injuries
  • Neostriatum / metabolism
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / pharmacology*
  • Parkinsonian Disorders / chemically induced
  • Parkinsonian Disorders / drug therapy*
  • Parkinsonian Disorders / metabolism
  • Parkinsonian Disorders / physiopathology
  • Placebos
  • Positron-Emission Tomography / methods
  • Random Allocation
  • Substantia Nigra / drug effects
  • Substantia Nigra / injuries
  • Substantia Nigra / metabolism
  • Treatment Outcome


  • Carboxylic Acids
  • Neuroprotective Agents
  • Placebos
  • carboxyfullerene C63(COOH)6
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Dopamine