Biomarkers of Pioglitazone Effects in Parkinson's Disease (BioPEP)

Objective/Rationale: 
Pioglitazone is a medication used to treat diabetes that that has shown promise in laboratory studies for potentially slowing the progression of Parkinson’s disease (PD). The goal of this study is to test blood and urine biomarkers of the effects of pioglitazone to provide insights as to the mechanisms of possible protection by pioglitazone, and to determine if we can predict which patients are likely to benefit most from pioglitazone treatment.

Project Description: 
In conjunction with an upcoming multicenter clinical study of pioglitazone supported by the National Institute of Neurological Disorders and Stroke (NINDS), we will collect blood and urine samples from participating PD subjects at baseline and again after fournd 10 months of treatment with pioglitazone. Levels of markers of oxidative stress and inflammation will be assessed, along with levels of expression of specific genes that are influenced by pioglitazone and thought to contribute to the protective effects of this agent. One such gene is called “PGC-1alpha,” which regulates the expression of many other genes, leading to enhanced energy metabolism and protection against oxidative stress.
 
Relevance to Diagnosis/Treatment of Parkinson’s Disease:  
Studies of agents that may slow progression of PD are difficult, in part due to the lack of proven objective biomarkers of the progression of PD. Identification of biomarkers of the impact of pioglitazone can improve the efficiency of clinical studies and may allow identification of subsets of patients who are particularly likely to benefit from pioglitazone. 

Anticipated Outcome: 
We predict that markers of oxidative stress and inflammation will be elevated in the blood and urine of PD patients, and that pioglitazone treatment will reduce levels of these markers. We further predict that pioglitazone will increase levels of expression of PGC-1alpha. The magnitude of the effect of pioglitazone on these biomarkers is predicted to correlate with the degree to which pioglitazone slows progression of PD.

• One Patient’s Perspective on Participating in the Pioglitazone Study