Effects of Chronic GM1 Ganglioside Treatment on Cognitieve and Motor Deficits in a Slowly Progressing Model of Parkinsonism in Non-Human Primates

Abstract

This study examined the effects of chronic GM1 ganglioside administration on the evolution of cognitive and motor deficits in monkeys exposed to low doses 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 MPTP for 26 weeks. Once stable cognitive deficits and minimal motor deficits were observed, animals were randomized to saline (N = 2) or GM1 ganglioside (N = 3) treatment groups. Treatments were administered for 90 weeks concurrent with continued low dose MPTP administration. During the first phase of the study (treatment 1-31), GM1 administration ameliorated cognitive deficits and protected against further cognitive decline. Cognitieve deficits worsened in saline-treated animals during this period. In the second phase of the study (weeks 32-52) MPTP dose were increased to enhance the severity of the parkinsonism. GM1-treated animals had delayed onset of motor deficits and a continued preservation of cognitive function. Cognitive and motor 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 during the intial phase of study. GM1-treated animals had significant recovery of motor function, while motor and cognitive function continued to be severely impaired in the saline-treated group. These results suggest that chronic GM1 treatment could be useful in the long-term treatment of Parkinson's disease.