Objective/Rationale:
Safety and effectiveness in brain delivery remain two major challenges in developing novel neuroprotective agents to treat Parkinson’s disease (PD) patients. This project will test whether insulin, when applied to nasal cavities, could protect dopamine neurons and alleviate motor deficits in a pre-clinical model of PD. The hypothesis is based on findings in human subjects showing that insulin can reach the brain via nasal cavities, and by cell culture work demonstrating that insulin is a potent protective agent for neurons.
Project Description:
A well-established pre-clinical PD model will be utilized, and the dopaminergic pathway will be lesioned. Insulin will be continuously applied to nasal cavities for 15 days, and two major outcome measures will be assessed to evaluate the therapeutic efficacy. A battery of motor behavioral tests will be performed on Day 8 and Day 15 post-lesion, followed by neuroanatomical studies to assess the integrity of dopaminergic system. The combined approaches at both structural and functional levels will give an objective evaluation of therapeutic potential of intranasal insulin in this particular pre-clinical PD model.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
The track record of long-term safety and the well-established brain delivery via nasal pathway make insulin stand out from other neuroprotective agents. If it shows to be effective in pre-clinical PD models, the timeline from clinical trial to patient use may be much shorter compared to other neuroprotective agents.
Anticipated Outcome:
Researchers expect that intranasal insulin will significantly improve motor deficits in this particular pre-clinical PD model and that observed functional recovery is associated with protection of dopaminergic neurons and/or nigrostriatal terminals. If this is true, it strongly suggests that insulin is a novel neurotrophic factor and should be tested in other pre-clinical models such as alpha-synuclein model.