This grant builds upon the research from a prior grant: Activation of Nrf2 neuroprotective pathways for Parkinson’s disease
Promising Outcomes of Original Grant:
In our original grant we assessed whether the antidiabetic compound pioglitazone can be neuroprotective in a non-human primate model of Parkinson’s disease. We proposed to test this compound because of its anti-inflammatory and anti-oxidative stress properties, and because pioglitazone has shown neuroprotective effects in pre-clinical models of PD.
Our results confirmed our hypothesis. When the PD non-human primates received oral pioglitazone, at a dose equivalent to the one used in the clinic to treat diabetic patients, we found that the treatment was able to induce moderate but significant functional and anatomical benefits.
Objectives for Supplemental Investigation:
In this new study our goal is to asess how much pioglitazone is in the cerebrospinal fluid after oral administration. This will be a short-term project carried out in normal non-human primates that will receive oral daily dosing of pioglitazone. We will test three different doses, all of them equivalent to the dosing used in the clinic to treat diabetic patients. The collected data will help understand pioglitazone avaialbility to the brain at different doses and how much is needed to induce neuroprotection.
Importance of This Research for the Development of a New PD Therapy:
The accumulated evidence strongly support clinical testing of pioglitazone’s potential to slow down PD progression. Responsible clinical translation requires to know brain penetrance of pioglitazone in primates to assist in the determination of CSF therapeutical levels of pioglitazone, information that it is currently missing. The data to be collected in this new study will help move forward this project and guide the dosing in a clinical trial.
Final Outcome
Our goal is to asess how much pioglitazone is in the cerebrospinal fluid after oral administration. This is a short-term project carried out in normal non-human primates that will receive oral daily dosing of pioglitazone. We are testing three different doses, all of them equivalent to the dosing used in the clinic to treat diabetic patients. The collected data will help understand pioglitazone availability to the brain at different doses and how much is needed to induce neuroprotection.