The immunophilin ligand GPI-1046 does not have neuroregenerative effects in MPTP-treated monkeys.
Nonimmunosuppressant immunophilin ligands have been shown to have neurotrophic properties in rodent models of Parkinson's disease (PD), although little is known about the effects of these ligands in primates. The immunophilin ligand, GPI-1046, promotes the regeneration of dopamine (DA) cells in association with functional recovery in rodent models. We explored the regenerative effects of GPI-1046 in an MPTP primate model of PD. We used single photon emission computed tomography (SPECT) and the DA transporter tracer (DAT), [(123)I]beta-CIT, to evaluate DAT density and clinical recovery before and after treatment with GPI-1046 or vehicle. Subsequent histological studies were also performed. No effects of GPI-1046 were found on any of these measures. These findings show that GPI-1046 does not have regenerative effects in MPTP-treated primates and suggest that there may be species differences with respect to the trophic effects of GPI-1046 on nigrostriatal DA neurons.
Eberling
Jamie L
JL
Department of Neurology and Center for Neuroscience, University of California, Davis, 95616, USA. jleberling@lbl.gov
Pivirotto
Phillip
P
Bringas
John
J
Steiner
Joseph P
JP
Kordower
Jeffrey H
JH
Chu
Yaping
Y
Emborg
Marina E
ME
Bankiewicz
Krzysztof S
KS
D000818:Animals; D020104:Immunophilins / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D008024:Ligands; D020267:MPTP Poisoning / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008253:Macaca mulatta; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D011759:Pyrrolidines / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use*
C104949:GPI 1046; D008024:Ligands; D011759:Pyrrolidines; D020104:Immunophilins