Evaluation of Drug

Abstract

Parkinson's disease (PD) is a hypokinetic, age-related movement disorder associated with chronic, progressive degeneration of dopaminergic neurons, with cell bodies located in the substantia nigra pars compacta (SNpc) and axon terminals in the striatum. Striatal depletion of the neurotransmitter dopamine (DA) gives rise to the cardinal PD motor symptoms. We utilized a 6-hydroxydopamine (6-OHDA) animal PD model to test the application of a preclinical drug candidate, drug "X", in ameliorating and/or preventing advanced parkinsonism in two studies. First, a neurorestoration study tested the efficacy of drug "X" in restoring motor functionality to animals in which the 6-OHDA lesion had fully developed. Second, a neuroprotection study assessed the effectiveness of drug "X" in preventing the initial development of the 6-OHDA lesion and the onset of motor impairments. Behavioral data indicate that there are no significant differences between the control and drug "X" groups in both studies, suggesting that drug "X" does not improve established severe PD motor deficits nor prevent their initial development. However, we are analyzing brain tissue harvested to 1) verify the extent of the lesion with stereology in the SNpc, 2) evaluate striatal DA levels, and 3) investigate any neuroprotective effects of drug "X" on nigral DAergic neurons.