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.
Keywords:
8-hydroxydeoxyguano sine; 8OHdG; IL-6; PGC-1alpha; Parkinson’s disease; biomarker; cytokine; inflammation; interleukin-6; oxidative stress; pioglitazone.
Publication types
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Clinical Trial, Phase II
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Randomized Controlled Trial
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Research Support, Non-U.S. Gov't
MeSH terms
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8-Hydroxy-2'-Deoxyguanosine
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Aged
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Biomarkers / blood
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Biomarkers / urine
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Deoxyguanosine / analogs & derivatives*
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Deoxyguanosine / urine
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Disease Progression*
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Female
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Gene Expression / drug effects
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Humans
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Hypoglycemic Agents / administration & dosage
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Hypoglycemic Agents / pharmacology*
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Inflammation / blood
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Interleukin-6 / blood*
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Male
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Middle Aged
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Oxidative Stress / drug effects
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Parkinson Disease* / blood
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Parkinson Disease* / drug therapy
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Parkinson Disease* / urine
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Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
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Pioglitazone
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Thiazolidinediones / administration & dosage
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Thiazolidinediones / pharmacology*
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Transcription Factors / blood*
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Treatment Failure
Substances
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Biomarkers
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Hypoglycemic Agents
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IL6 protein, human
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Interleukin-6
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PPARGC1A protein, human
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Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
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Thiazolidinediones
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Transcription Factors
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8-Hydroxy-2'-Deoxyguanosine
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Deoxyguanosine
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Pioglitazone