Peripheral Biomarkers of Parkinson’s Disease Progression and Pioglitazone Effects

Article type: Short Communication

Authors: Simon, David K.^{a; *} | Simuni, Tanya^b | Elm, Jordan^c | Clark-Matott, Joanne^a | Graebner, Allison K.^a | Baker, Liana^d | Dunlop, Susan R.^e | Emborg, Marina^f | Kamp, Cornelia^g | Morgan, John C.^h | Ross, G. Websterⁱ | Sharma, Saloni^d | Ravina, Bernard^j | On behalf of the NINDS NET-PD Investigators

Affiliations: [a] Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA | [b] Neurology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA | [c] Biostatistics, Medical University of South Carolina, Charleston, SC, USA | [d] Clinical Trials Coordination Center, University of Rochester, Medical Center, Rochester, NY, USA | [e] Neurology, Johns Hopkins University, Baltimore, MD, USA | [f] Wisconsin National Primate Research Center and Department of Medical Physics, University of Wisconsin, Madison, WI, USA | [g] Clinical Materials Services Unit, University of Rochester, Medical Center, Rochester, NY, USA | [h] Neurology, Medical College of Georgia, Augusta, GA, USA | [i] Neurology, Veterans Affairs Pacific Islands Health Care System, Honolulu, HI, USA | [j] Voyager Therapeutics, Inc., Cambridge, MA, USA

Correspondence: [*] Correspondence to: David K. Simon, MD, PhD, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Room CLS-638, Boston, 02215 MA, USA. Tel.: +1 617 735 3251; Fax: +1 617 735 2826; E-mail: [email protected]

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: PGC-1alpha, oxidative stress, inflammation, Parkinson’s disease, biomarker, pioglitazone, 8-hydroxydeoxyguano sine, 8OHdG, IL-6, interleukin-6, cytokine

DOI: 10.3233/JPD-150666

Journal: Journal of Parkinson's Disease, vol. 5, no. 4, pp. 731-736, 2015