Cerium Oxide Nanoparticles in the Treatment of Parkinson’s Disease – Toxicity and Biodistribution Studies

Promising Outcomes of Original Grant:
In our prior years of funding from The Michael J. Fox Foundation, we tested the hypothesis that cerium oxide nanoparticles (CeONP) were a disease-modifying therapy for PD. During this time, we found that CeONP:

• Promote growth of dopaminergic neurons in the substantia nigra
• Protect neurons from the dopaminergic deficits associated with the MPTP model of PD, when administered before or after MPTP challenge
• Preserve striatal dopamine and dopaminergic neurons in the MPTP-pre-clinical model
• Decrease basal levels of lipid peroxidation in the brain

Objectives for Supplemental Investigation:
Based on these very promising results, our supplemental investigation proposes to conduct studies that will enable the filing of an Investigational New Drug application, to further move CeONP down the drug development pipeline.  Prior to a drug being tested for human use, safety, toxicity, and pharmacokinetic studies need to be performed to assure the drug will be relatively safe. We will conduct these studies in our supplemental investigation.  Immediate safety and toxicity will be assessed at two doses. Additionally, we will determine how CeONP are distributed in the body and determine what organs they accumulate in. We will examine tissues for histopathology and adverse effects. Further, since nanoparticles may persist in the system after initial delivery, we will also examine histopathology and biodistribution at six months after administration.

Importance of This Research for the Development of a New PD Therapy:
Prior to a drug being tested in humans, information on safety, toxicity, and biodistribution must be known.  One must be comfortable in knowing that the potential drug is “relatively safe.” This research will provide the necessary safety, toxicity, and pharmacokinetic information necessary to move CeONP down the road from bench to bedside and eventual human use.