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Parkinson’s Disease
Volume 2012, Article ID 969418, 8 pages
http://dx.doi.org/10.1155/2012/969418
Research Article

17 -Ethynyl-androst-5-ene-3 ,7 ,17 -triol (HE3286) Is Neuroprotective and Reduces Motor Impairment and Neuroinflammation in a Murine MPTP Model of Parkinson’s Disease

1Department of Biomedical Sciences, School of Medicine, University of Catania, Via Androne 81, 95124 Catania, Italy
2Department of Immunobiology, Biomedical Primate Research Centre, Lange Kleiweg 161, 2288 GJ Rijswijk, The Netherlands
3Harbor Therapeutics, Inc., 9191 Towne Centre Drive, Suite 409, San Diego, CA 92122, USA
4Tumor Vaccine Group, School of Medicine, University of Washington, Seattle, WA 98109, USA

Received 26 April 2012; Revised 21 August 2012; Accepted 21 August 2012

Academic Editor: Heinz Reichmann

Copyright © 2012 Ferdinando Nicoletti et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

17α-Ethynyl-androst-5-ene-3β,7β,17β-triol (HE3286) is a synthetic androstenetriol in Phase II clinical development for the treatment of inflammatory diseases. HE3286 was evaluated for blood-brain barrier (BBB) permeability in mice, and efficacy in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) murine model of Parkinson’s disease (PD). We found that HE3286 freely penetrated the BBB. HE3286 treatment significantly improved motor function compared to vehicle in the rotarod test (mean 58.2 sec versus 90.9 sec, ), and reduced inflammatory mediator gene expression in the brain (inducible nitric oxide synthase, 20%, ; tumor necrosis factor α, 40%, , and interleukin-1β, 33%, ) measured by reverse-transcriptase polymerase chain reaction. Brain tissue histopathology and immunohistochemistry showed that HE3286 treatment increased the numbers of tyrosine hydroxylase-positive cells by 17% compared to vehicle ( ), and decreased the numbers of damaged neurons by 38% relative to vehicle ( ). L-3,4-dihydroxyphenylalanine (L-DOPA) efficacy was not enhanced by concurrent administration of HE3286. HE3286 administration prior to MPTP did not enhance efficacy. Our data suggest a potential role for HE3286 in PD treatment, and provides incentive for further investigation.