Effects of chronic GM1 ganglioside treatment on cognitive and motor deficits in a slowly progressing model of Parkinsonism in non-human primates

This study examined the effects of chronic GM1 ganglioside administration o n the evolution of cognitive and motor deficits in monkeys exposed to low d oses of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) over an extended period of time. Monkeys were administered low doses of MPT P for 26 weeks. Once stable cognitive deficits and minimal motor deficits w ere observed, animals were randomized to saline (N = 2) or GM1 ganglioside (N = 3) treatment groups. Treatments were administered for 90 weeks concurr ent with continued low dose MPTP administration. During the first phase of the study (treatment weeks 1-31), GM1 administration ameliorated cognitive deficits and protected against further cognitive decline. Cognitive deficit s worsened in saline-treated animals during this period. In the second phas e of the study (weeks 32-52) MPTP doses were increased to enhance the sever ity of the parkinsonism. GM1-treated animals had delayed onset of motor def icits and a continued preservation of cognitive function. Cognitive and mot or function declined in the saline-treated group. In the final phase of the study (weeks 53-90), MPTP doses were lowered back to the levels used durin g the initial phase of the study. GM1-treated animals had significant recov ery of motor function, while motor and cognitive function continued to be s everely impaired in the saline-treated group. These results suggest that ch ronic GM1 treatment could be useful in the long-term treatment of Parkinson 's disease.