Literature DB >> 20704560

Why so few drugs for Alzheimer's disease? Are methods failing drugs?

R E Becker1, N H Greig.   

Abstract

Recent studies of Alzheimer's disease (AD) and other neuropsychiatric drug developments raise questions whether failures of some drugs occur due to flaws in methods. In three case studies of recent AD drug development failures with phenserine, metrifonate, and tarenflurbil we identified methodological lapses able to account for the failures. Errors in complex systems such as drug developments are both almost inescapable due to human mistakes and most frequently hidden at the time of occurrence and thereafter. We propose preemptive error management as a preventive strategy to exclude or control error intrusions into neuropsychiatric drug developments. We illustrate the functions we anticipate for a preemptive error management preventive strategy with a checklist and identify the limitations of this aspect of the proposal with three drug examples. This strategy applies core scientific practices to insure the quality of data within the current context of AD drug development practices.

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Year:  2010        PMID: 20704560      PMCID: PMC3010269          DOI: 10.2174/156720510793499075

Source DB:  PubMed          Journal:  Curr Alzheimer Res        ISSN: 1567-2050            Impact factor:   3.498


  27 in total

1.  The hunt for drugs to modify Alzheimer's disease.

Authors:  James Butcher
Journal:  Lancet Neurol       Date:  2007-12       Impact factor: 44.182

Review 2.  Alzheimer's disease drug development in 2008 and beyond: problems and opportunities.

Authors:  Robert E Becker; Nigel H Greig
Journal:  Curr Alzheimer Res       Date:  2008-08       Impact factor: 3.498

3.  What we have learned from the Myriad trials.

Authors:  S B Hendrix; G K Wilcock
Journal:  J Nutr Health Aging       Date:  2009-04       Impact factor: 4.075

Review 4.  Dimebon as a potential therapy for Alzheimer's disease.

Authors:  Rachelle S Doody
Journal:  CNS Spectr       Date:  2009-08       Impact factor: 3.790

5.  Pharmacology. The puzzling rise and fall of a dark-horse Alzheimer's drug.

Authors:  Greg Miller
Journal:  Science       Date:  2010-03-12       Impact factor: 47.728

6.  Effect of tarenflurbil on cognitive decline and activities of daily living in patients with mild Alzheimer disease: a randomized controlled trial.

Authors:  Robert C Green; Lon S Schneider; David A Amato; Andrew P Beelen; Gordon Wilcock; Edward A Swabb; Kenton H Zavitz
Journal:  JAMA       Date:  2009-12-16       Impact factor: 56.272

Review 7.  Why do so many drugs for Alzheimer's disease fail in development? Time for new methods and new practices?

Authors:  Robert E Becker; Nigel H Greig; Ezio Giacobini
Journal:  J Alzheimers Dis       Date:  2008-10       Impact factor: 4.472

8.  Neuropsychiatric clinical trials: should they accommodate real-world practices or set standards for clinical practices?

Authors:  Robert E Becker; Nigel H Greig
Journal:  J Clin Psychopharmacol       Date:  2009-02       Impact factor: 3.153

9.  Effect of tramiprosate in patients with mild-to-moderate Alzheimer's disease: exploratory analyses of the MRI sub-group of the Alphase study.

Authors:  S Gauthier; P S Aisen; S H Ferris; D Saumier; A Duong; D Haine; D Garceau; J Suhy; J Oh; W Lau; J Sampalis
Journal:  J Nutr Health Aging       Date:  2009-06       Impact factor: 4.075

10.  The perils of Alzheimer's drug development.

Authors:  Lon S Schneider; Debomoy K Lahiri
Journal:  Curr Alzheimer Res       Date:  2009-02       Impact factor: 3.498

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  22 in total

1.  Functional activity of the novel Alzheimer's amyloid β-peptide interacting domain (AβID) in the APP and BACE1 promoter sequences and implications in activating apoptotic genes and in amyloidogenesis.

Authors:  Jason A Bailey; Bryan Maloney; Yuan-Wen Ge; Debomoy K Lahiri
Journal:  Gene       Date:  2011-06-25       Impact factor: 3.688

2.  Advances in understanding Alzheimer's disease, and the contributions of current Alzheimer research: ten years on and beyond.

Authors:  Nigel H Greig; Debomoy K Lahiri
Journal:  Curr Alzheimer Res       Date:  2014-02       Impact factor: 3.498

Review 3.  Advances in microRNA experimental approaches to study physiological regulation of gene products implicated in CNS disorders.

Authors:  Justin M Long; Debomoy K Lahiri
Journal:  Exp Neurol       Date:  2012-01-05       Impact factor: 5.330

Review 4.  Linking Alzheimer's disease and type 2 diabetes mellitus via aberrant insulin signaling and inflammation.

Authors:  Mohammad A Kamal; Shubha Priyamvada; Arivarasu N Anbazhagan; Nasimudeen R Jabir; Shams Tabrez; Nigel H Greig
Journal:  CNS Neurol Disord Drug Targets       Date:  2014-03       Impact factor: 4.388

5.  Why do trials for Alzheimer's disease drugs keep failing? A discontinued drug perspective for 2010-2015.

Authors:  Dev Mehta; Robert Jackson; Gaurav Paul; Jiong Shi; Marwan Sabbagh
Journal:  Expert Opin Investig Drugs       Date:  2017-06       Impact factor: 6.206

6.  Fire in the ashes: can failed Alzheimer's disease drugs succeed with second chances?

Authors:  Robert E Becker; Nigel H Greig
Journal:  Alzheimers Dement       Date:  2012-03-30       Impact factor: 21.566

7.  Synergistic inhibition of butyrylcholinesterase by galantamine and citalopram.

Authors:  Ryan Walsh; Kenneth Rockwood; Earl Martin; Sultan Darvesh
Journal:  Biochim Biophys Acta       Date:  2011-08-19

Review 8.  Lost in translation: neuropsychiatric drug development.

Authors:  Robert E Becker; Nigel H Greig
Journal:  Sci Transl Med       Date:  2010-12-08       Impact factor: 17.956

Review 9.  Alzheimer disease therapy--moving from amyloid-β to tau.

Authors:  Ezio Giacobini; Gabriel Gold
Journal:  Nat Rev Neurol       Date:  2013-11-12       Impact factor: 42.937

10.  Was phenserine a failure or were investigators mislead by methods?

Authors:  Robert E Becker; Nigel H Greig
Journal:  Curr Alzheimer Res       Date:  2012-12       Impact factor: 3.498

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