Nature Reviews Drug Discovery contents September 2012 Volume 11 Number 9 pp 653-730

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TABLE OF CONTENTS
September 2012 Volume 11 Number 9		Advertisement
Impact Factor 29.008 *	In this issue Comment News and Analysis Research Highlights Reviews Correspondence Also this month  Featured article: Autophagy modulation as a potential therapeutic target for diverse diseases David C. Rubinsztein, Patrice Codogno & Beth Levine	Microplate Reader Infinite® M1000 PRO • 10 detection modes • Including AlphaScreen®/ • AlphaLISA® • Excitation, emission, • absorbance, luminescence • and 3D scans • Flexible wavelength • selection • Adjustable fluorescence • bandwidth settings • Free definition of plate • formats up to 1536-wells • NanoQuant Plate™ • compatible Click here for details
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In this issue p653 | doi:10.1038/nrd3839 Full Text
Comment: Down's syndrome and Alzheimer's disease: towards secondary prevention Seth Ness, Michael Rafii, Paul Aisen, Michael Krams, Wayne Silverman & Husseini Manji p655 | doi:10.1038/nrd3822 A public-private partnership to establish biomarkers of dementia in Down's syndrome could aid the development of preventive therapies for the dementia associated with both Down's syndrome and Alzheimer's disease, based on the apparent common role of amyloid precursor protein in the two conditions. Abstract | Full Text | PDF
NEWS AND ANALYSIS		Top
Sting of Alzheimer's failures offset by upcoming prevention trials Asher Mullard p657 | doi:10.1038/nrd3842 Three prevention trials in asymptomatic Alzheimer's disease patients will attempt to validate the amyloid hypothesis, evaluate biomarkers and set the stage for drug approvals. PDF
Europe sets out to reform its clinical trial rules Daniel Cressey p660 | doi:10.1038/nrd3843 A proposal to replace widely criticized trial regulations could boost European drug development, if key details can be sorted out. PDF
NEWS IN BRIEF Novartis revs the CAR immunotherapies | New hope for anti-inflammatory p38 inhibitors? | Sepsis field set back again p663 | doi:10.1038/nrd3840 PDF
BIOBUSINESS BRIEFS Regulatory watch: Pioneering gene therapy on brink of approval Alexandra Flemming p664 | doi:10.1038/nrd3835 PDF
BIOBUSINESS BRIEFS Trial watch: HIV integrase inhibitor-based regimen beats market leader Sarah Crunkhorn p664 | doi:10.1038/nrd3836 PDF
PATENT WATCH Extra exclusivity for new medical uses | Post-approval testing shielded from patent infringement | Autophagy modulation Charlotte Harrison p666 | doi:10.1038/nrd3841 PDF
AN AUDIENCE WITH Mark McClellan p668 | doi:10.1038/nrd3837 Mark McClellan, Director of the Brookings Institution's health care reform centre, discusses the need for better metrics to measure the health of biomedical innovation. PDF
FROM THE ANALYST'S COUCH The pharmaceutical market for obesity therapies Donny Wong, Kate Sullivan & Gideon Heap p669 | doi:10.1038/nrd3830 In the wake of the recent approvals of the first new obesity therapies in more than a decade, Wong and colleagues analyse their market prospects as well as the late-stage pipeline. PDF
RESEARCH HIGHLIGHTS Top Cancer: Passenger deletions create cancer-specific Achilles heel p671 | doi:10.1038/nrd3826 PDF Structure-based drug design: Opening the door to an epigenetic target p672 | doi:10.1038/nrd3827 PDF Ischaemic disorders: Nanotherapeutic delivers clot-busting drug p672 | doi:10.1038/nrd3828 PDF Vaccination: Oral vaccine induces genitorectal immunity p673 | doi:10.1038/nrd3844 PDF Antisense therapeutics: Nuclear RNA more susceptible to knockdown p674 | doi:10.1038/nrd3825 PDF IN BRIEF Amyloid diseases: Targeting filamin A reduces Alzheimer's signalling | HIV: Waking up latent HIV | Anticancer drugs: Reactivating p53 tumour suppressor function PDF Drug Discovery JOBS of the week Internships - SAS, Clinical Research, Pharma Research, Clinical Data Management CDM, Oracle Clinical OC / RDC, Bioinformatics & Drug Design – Training with Live Project and Placement Assistance : Medwin Hospitals BioMed Informatics Medwin Hospitals Research Associate US Food and Drug Administration Post Doctoral Fellowship Scheme Centre for Drug Research Sr. Associate Scientist / Scientist, Cell Culture – Cystic Pfizer Early Career Scientists and Engineers: Computational Biochemistry Research Group D. E. Shaw Research, LLC More Science jobs from Drug Discovery EVENT 25th Annual Mouse Molecular Genetics Conference 02.-06.10.12 CA, US More science events from
REVIEWS		Top
Limitations in anti-obesity drug development: the critical role of hunger-promoting neurons Marcelo O. Dietrich & Tamas L. Horvath p675 | doi:10.1038/nrd3739 Effective and safe pharmacological options for the prevention and treatment of obesity remain elusive. Here, Dietrich and Horvath review the role of the hypothalamus in the control of food intake and the mechanism of action of current anti-obesity agents. They propose that targeting hunger pathways, such as those activated during calorie restriction and exercise, might lead to safer long-term obesity therapies. Abstract | Full Text | PDF
Leptin revisited: its mechanism of action and potential for treating diabetes Roberto Coppari & Christian Bjorbaek p692 | doi:10.1038/nrd3757 Disappointing clinical trials halted progress in using leptin for the treatment of obesity. Here, the authors propose a role for leptin in the treatment of type 1 diabetes and postulate that if the mechanisms of leptin resistance are better understood, leptin may become an important adjunct tool for the treatment of type 2 diabetes. Abstract | Full Text | PDF
Autophagy modulation as a potential therapeutic target for diverse diseases David C. Rubinsztein, Patrice Codogno & Beth Levine p709 | doi:10.1038/nrd3802 The lysosomal degradation pathway known as autophagy has an essential homeostatic role in controlling the quality of the cytoplasm. However, this pathway has also been implicated in the pathology of an array of human disorders. Here, Rubinsztein and colleagues provide an overview of the mechanisms and regulation of autophagy, discuss the role of this pathway in disease and highlight potential strategies for therapeutic modulation. Abstract | Full Text | PDF
CORRESPONDENCE		Top
Correspondence: Shouldn't enantiomeric purity be included in the 'minimum information about a bioactive entity'? Giovanni Lentini p730 | doi:10.1038/nrd3503-c1 Full Text | PDF
AUTHOR REPLY		Top
Author reply: Shouldn't enantiomeric purity be included in the 'minimum information about a bioactive entity? Response from the MIABE group Sandra Orchard, Bissan Al-Lazikani, Steve Bryant, Dominic Clark, Elizabeth Calder, Ian Dix, Ola Engkvist, Mark Forster, Anna Gaulton, Michael Gilson, Robert Glen, Martin Grigorov, Kim Hammond-Kosack, Lee Harland, Andrew Hopkins, Christopher Larminie, Nick Lynch, Romeena K. Mann, Peter Murray-Rust, Elena Lo Piparo, Christopher Southan, Christoph Steinbeck, David Wishart, Henning Hermjakob, John Overington & Janet Thornton p730 | doi:10.1038/nrd3503-c2 Full Text | PDF
Corrigendum: PDUFA V goes back to basics Asher Mullard p730 | doi:10.1038/nrd3824 Full Text | PDF
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