PBT2 rapidly improves cognition in Alzheimer's Disease: additional phase II analyses.
- PubMed: 20164561
Abstract
PBT2 is a copper/zinc ionophore that rapidly restores cognition in mouse models of Alzheimer's disease (AD). A recent Phase IIa double-blind, randomized, placebo-controlled trial found that the 250 mg dose of PBT2 was well-tolerated, significantly lowered cerebrospinal fluid (CSF) levels of amyloid-beta42, and significantly improved executive function on a Neuro-psychological Test Battery (NTB) within 12 weeks of treatment in patients with AD. In the post-hoc analysis reported here, the cognitive, blood marker, and CSF neurochemistry outcomes from the trial were subjected to further analysis. Ranking the responses to treatment after 12 weeks with placebo, PBT2 50 mg, and PBT2 250 mg revealed that the proportions of patients showing improvement on NTB Composite or Executive Factor z-scores were significantly greater in the PBT2 250 mg group than in the placebo group. Receiver-operator characteristic analyses revealed that the probability of an improver at any level coming from the PBT2 250 mg group was significantly greater, compared to placebo, for Composite z-scores (Area Under the Curve AUC =0.76, p=0.0007), Executive Factor z-scores (AUC =0.93, p=1.3 x 10(-9)), and near-significant for the ADAS-cog (AUC =0.72, p=0.056). There were no correlations between changes in CSF amyloid-beta or tau species and cognitive changes. These findings further encourage larger-scale testing of PBT2 for AD.
Author-supplied keywords
PBT2 rapidly improves cognition in Alzheimer's Disease: additional phase II analyses.
Journal of Alzheimer’s Disease
ISSN: 1387-2877
IOS Press
DOI: 10.3233/JAD-2010-1390
PBT2 Rapidly Improves Cognition in Alzheimer’s Disease: Additional Phase II Analyses
Noel G. Fauxa, Craig W. Ritchieb, Adam Gunna, Alan Rembacha,c, Andrew Tsatsanisa, Justin
Bedod, John Harrisone, Lars Lannfeltf, Kaj Blennowg, Henrik Zetterbergg, Martin Ingelssonf,
Colin L. Mastersa, Rudolph E. Tanzih, Jeffrey L. Cummingsj, Caroline M. Herdk and Ashley I.
Busha
aMental Health Research Institute, The University of Melbourne, Parkville, Victoria, Australia
bDepartment of Psychological Medicine, Imperial College London, London, UK
cCSIRO Parkville, Victoria, Australia
dVictorian Research Laboratory, National ICT of Australia (NICTA)
eCogState Ltd, Warminster, UK
fDepartment of Public Health / Geriatrics, Uppsala University Hospital, Uppsala, Sweden
gClinical Neurochemistry Laboratory, Sahlgren’s University Hospital, Mölndal, Sweden
hGenetics and Aging Research Unit, Massachusetts General Hospital, Boston, MA, USA
iMary S. Easton Center for Alzheimer’s Disease Research at UCLA, Los Angeles, CA, USA
jPrana Biotechnology Ltd, Parkville, Victoria, Australia
kDepartment of Pathology, The University of Melbourne, Parkville, Victoria, Australia
Running title: PBT2 rapidly improves Alzheimer’s disease
Accepted 11 January 2010
Correspondence to: Professor Ashley I. Bush, The Mental Health Research Institute, 155 Oak
Street, Parkville, Victoria 3052, Australia; Tel: +61 3 9389 2962, Fax: +61 3 9387 5061, Email:
a.bush@mhri.edu.au.
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