title: Peripheral Biomarkers of Parkinson's Disease Progression and Pioglitazone Effects.
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.
authors.affiliation: Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
authors.forename: David K
authors.initials: DK
authors.lastname: Simon
authors.affiliation: Neurology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Tanya
authors.initials: T
authors.lastname: Simuni
authors.affiliation: Biostatistics, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Jordan
authors.initials: J
authors.lastname: Elm
authors.affiliation: Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
authors.forename: Joanne
authors.initials: J
authors.lastname: Clark-Matott
authors.affiliation: Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
authors.forename: Allison K
authors.initials: AK
authors.lastname: Graebner
authors.affiliation: Clinical Trials Coordination Center, University of Rochester, Medical Center, Rochester, NY, USA.
authors.forename: Liana
authors.initials: L
authors.lastname: Baker
authors.affiliation: Neurology, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Susan R
authors.initials: SR
authors.lastname: Dunlop
authors.affiliation: Wisconsin National Primate Research Center and Department of Medical Physics, University of Wisconsin, Madison, WI, USA.
authors.forename: Marina
authors.initials: M
authors.lastname: Emborg
authors.affiliation: Clinical Materials Services Unit, University of Rochester, Medical Center, Rochester, NY, USA.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Kamp
authors.affiliation: Neurology, Medical College of Georgia, Augusta, GA, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Morgan
authors.affiliation: Neurology, Veterans Affairs Pacific Islands Health Care System, Honolulu, HI, USA.
authors.forename: G Webster
authors.initials: GW
authors.lastname: Ross
authors.affiliation: Clinical Trials Coordination Center, University of Rochester, Medical Center, Rochester, NY, USA.
authors.forename: Saloni
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Voyager Therapeutics, Inc., Cambridge, MA, USA.
authors.forename: Bernard
authors.initials: B
authors.lastname: Ravina
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000652:urine; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000652:urine; D018450:Disease Progression; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007249:Inflammation / Q000097:blood; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D010300:Parkinson Disease / Q000097:blood / Q000188:drug therapy / Q000652:urine; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000494:pharmacology*; D014157:Transcription Factors / Q000097:blood*; D017211:Treatment Failure
chemical_list: D015415:Biomarkers; D007004:Hypoglycemic Agents; C508600:IL6 protein, human; D015850:Interleukin-6; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D045162:Thiazolidinediones; D014157:Transcription Factors; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D000077205:Pioglitazone
keywords: 8-hydroxydeoxyguano sine; 8OHdG; IL-6; PGC-1alpha; Parkinson’s disease; biomarker; cytokine; inflammation; interleukin-6; oxidative stress; pioglitazone