'Biomarkers' in body fluids might be able to help researchers determine whether a new treatment for PD is effective at slowing the disease process. Pioglitazone is a drug usually used to treat diabetes, which was recently trialled in patients with PD to see if it might help slow disease progression. Unfortunately, the trial did not show any effect on disease progression judged by traditional 'clinical' markers.

In this new study, researchers have used blood-based biomarkers of inflammation and oxidative DNA damage to assess whether pioglitazone might be having a neuroprotective effect that was not clinically detectable in the original clinical trial. Pioglitazone did not alter the biomarker levels, suggesting protect against oxidative stress and inflammation in PD.

This is an interesting example of how body fluid biomarkers can be used to assess whether a potentially neuroprotective agent might be working as expected. However, the blood biomarkers used here are not particularly well validated -- they may not be very specific to PD and their precise relationship with disease progression remains undetermined. Of note, for the patients in this study, baseline levels of the biomarkers and changes in the biomarkers were not associated with rate of disease progression. As a result, it is still difficult to draw conclusions about pioglitazone's efficacy as a disease-modifying drug, despite the negative results of this study.

Peripheral Biomarkers of Parkinson's Disease Progression and Pioglitazone Effects.

Simon DK, Simuni T, Elm J, Clark-Matott J, Graebner AK, Baker L, Dunlop SR, Emborg M, Kamp C, Morgan JC, Ross GW, Sharma S, Ravina B

Abstract: Pioglitazone, an oral hypoglycemic agent, recently failed to show promise as a disease-modifying agent in a 44-week phase 2 placebo-controlled study in 210 Parkinson’s disease (PD) subjects. We analyzed peripheral biomarkers, including leukocyte PGC-1α and target gene expression, plasma interleukin 6 (IL-6) as a marker of inflammation, and urine 8-hydroxydeoxyguanosine (8OHdG) as a marker of oxidative DNA damage. Baseline or changes from baseline in biomarker levels were not associated with the rate of progression of PD. Pioglitazone did not significantly alter biomarker levels. Other agents that more effectively target these mechanisms remain of potential interest as disease modifying therapies in PD.

DOI: 10.3233/JPD-150666

Journal: Journal of Parkinson's Disease, 

Published 3 October 2015

Simon DK, Simuni T, Elm J, Clark-Matott J, Graebner AK, Baker L, Dunlop SR, Emborg M, Kamp C, Morgan JC, Ross GW, Sharma S, & Ravina B (2015). Peripheral Biomarkers of Parkinson's Disease Progression and Pioglitazone Effects. Journal of Parkinson's disease PMID: 26444095