Funded Studies
This grant builds upon the research from a prior grant: Cerium Oxide Nanoparticles in Treatment of Parkinson's Disease
Promising Outcomes of Original Grant:
In our 2009-2010 proposal, we hypothesized that pretreatment of a pre-clinical model with cerium oxide nanoparticles would be neuroprotective in the MPTP-pre-clinical model of Parkinson’s disease. We found that treatment of the model with cerium oxide nanoparticles appeared to increase striatal dopamine as well as the numbers of neurons in the substantia nigra. When pre-clinical models treated with cerium oxide nanoparticles were subsequently exposed to MPTP to induce Parkinson’s disease, we found that cerium oxide nanoparticles dramatically preserved dopaminergic neurons and striatal dopamine content. Our results suggest that these nanoparticles may be potent neuroprotective agents in Parkinson’s disease.
Objectives for Supplemental Investigation:
Although cerium oxide nanoparticles were neuroprotective when administered prior to the insult that mimics Parkinson’s disease, it is critical to determine whether neuroprotection is afforded after the disease develops. In the current phase, we will administer cerium oxide nanoparticles after challenge with MPTP, and assess neuroprotection. This is a next logical step in moving this agent to potential use in treatment of Parkinson’s disease.
Importance of This Research for the Development of a New PD Therapy:
Cerium oxide nanoparticles are novel “nanopharmaceuticals” that hold potential for changing outcomes and improving treatment of Parkinson’s disease. If successful, this work will provide the foundation necessary to move cerium oxide nanoparticles further along the route from lab bench to patient bedside.
Final Outcome
Our group has previously found that cerium oxide nanoparticles preserve striatal dopamine and dopaminergic neurons in the substantia nigra, when delivered as a pretreatment in a pre-clinical model of Parkinson’s disease. In the current project, we found that cerium oxide nanoparticles were also effective in preserving striatal dopamine when delivered after the development of the disease. Our studies also suggest that cerium oxide nanoparticles may promote the growth of new dopaminergic neurons, and reduce oxidative stress in the brain. We also conducted dose response studies, and deteined an optimal dose for neuroprotection. These studies suggest that CeONP are a promising nanopharmaceutical that may alter the course of Parkinson’s Disease in the future.
Patents
Work supported the following patent application in progress:
WO 2009/052295 A2 Rzigalinski BA, Cohen CA, & Singh N. Cerium oxide nanoparticles for treatment and prevention of Alzheimer’s Disease, Parkinson’s Disease, and disorders associated with free radical production and/or mitochondrial dysfunction.
Publications:
1. Billings MA, Dillon C, Hockey KS, & Rzigalinski BA (2011) Cerium oxide nanoparticles protect against MPTP-induced dopaminergic neurodegeneration in a pre-clinical model for Parkinson’s Disease, J. Nanotechnology, in press.
Presentations:
1. Patent Presentation: Rzigalinski BA, Cerium oxide nanoparticles for treatment and prevention of Alzheimer’s disease, Parkinson’s disease, and disorders associated with free radical production and/or mitochondrial dysfunction., presented at IP section, Nanotechnology 2010, Boston, MA
2. Billings MA, Dillon C, Hockey KS, & Rzigalinski BA (2011) Cerium oxide nanoparticles protect against MPTP-induced dopaminergic neurodegeneration in a pre-clinical model of Parkinson’s Disease, American Osteopathic Association Annual Meeting, October 2011
PARTNERING PROGRAM
This grant was selected by The Michael J. Fox Foundation staff to be highlighted via the Foundation’s Partnering Program.