Protective efficacy of P7C3-S243 in the 6-hydroxydopamine model of Parkinson's disease

There are currently no therapeutic options for patients with Parkinson's disease that prevent or slow the death of dopaminergic neurons. We have recently identified the novel P7C3 class of neuroprotective molecules that blocks neuron cell death. The aim of this study was to determine whether treatment with highly active members of the P7C3 series blocks dopaminergic neuron cell death and associated behavioral and neurochemical deficits in the rat 6-hydroxydopamine (6-OHDA) model of Parkinson's disease. After unilateral injection of 6-OHDA into the median forebrain bundle, rats were assessed for behavioral function in the open field, cylinder test, and amphetamine-induced circling test. Thereafter, their brains were subjected to neurochemical and immunohistochemical analysis of dopaminergic neuron survival. Analysis was conducted as a function of treatment with P7C3 compounds, with administration initiated either before or after 6-OHDA exposure. Animals administered P7C3-A20 or P7C3-S243, two of the most advanced agents in the P7C3 series of neuroprotective compounds, both before and after 6-OHDA exposure showed evidence of protective efficacy in all measures. When P7C3-S243 administration was initiated after 6-OHDA exposure, rats also showed protective efficacy in all measures, which included blocking dopaminergic neuron cell death in ipsilateral substantia nigra pars compacta, preservation of dopamine and its metabolites in ipsilateral striatum, and preservation of normal motor behavior. The P7C3 series of compounds may form the basis for developing new therapeutic agents for slowing or preventing progression of Parkinson's disease. A newly characterized molecule helps to protect vulnerable brain cells and stave off symptoms in a rat model of Parkinson's disease. This progressive and incurable disorder occurs when neurons in the brain that make the signaling molecule dopamine die off, leading to movement problems and other symptoms. Andrew Pieper from the University of Iowa Carver College of Medicine, United States, and colleagues injected a neuroprotective molecule called P7C3-S243 into rats with the 6-hydroxydopamine-induced version of the disorder. Interestingly, they found the rats' dopamine-producing neurons stayed alive and that the rats themselves did not succumb to the expected motor problems. While current drug treatments — which lose efficacy over time — work by boosting dopamine levels, the new molecule increases cellular energy levels and could prove advantageous because it prevents vital neurons from dying in the first place.