Literature DB >> 23943247

Successes and failures for drugs in late-stage development for Alzheimer's disease.

Camryn Berk1, Marwan N Sabbagh.   

Abstract

To date, symptomatic medications prevail as the mainstay of treatment options for Alzheimer's disease (AD). There have been tremendous investments made to increase the numbers of drugs approved and the targets engaged, in an effort to alter the disease course or pathophysiology of AD. Unfortunately, almost all studies have not met expectations and no new drug (beyond medical foods) has been approved for the treatment of AD in the last decade. This review is a comparison of novel AD therapies in the late phases of clinical testing, including recent high-profile clinical failures, and agents in development with relatively unexplored mechanisms of action, with a focus on their potential as therapeutic agents and their proposed advantages over the treatments currently in use.

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Year:  2013        PMID: 23943247      PMCID: PMC4000701          DOI: 10.1007/s40266-013-0108-6

Source DB:  PubMed          Journal:  Drugs Aging        ISSN: 1170-229X            Impact factor:   3.923


  42 in total

1.  Amyloid-β contributes to blood-brain barrier leakage in transgenic human amyloid precursor protein mice and in humans with cerebral amyloid angiopathy.

Authors:  Anika M S Hartz; Björn Bauer; Emma L B Soldner; Andrea Wolf; Sandra Boy; Roland Backhaus; Ivan Mihaljevic; Ulrich Bogdahn; Hans H Klünemann; Gerhard Schuierer; Felix Schlachetzki
Journal:  Stroke       Date:  2011-11-23       Impact factor: 7.914

2.  Regulatory review of novel therapeutics--comparison of three regulatory agencies.

Authors:  Nicholas S Downing; Jenerius A Aminawung; Nilay D Shah; Joel B Braunstein; Harlan M Krumholz; Joseph S Ross
Journal:  N Engl J Med       Date:  2012-05-16       Impact factor: 91.245

Review 3.  RAGE: a potential target for Abeta-mediated cellular perturbation in Alzheimer's disease.

Authors:  Xi Chen; Douglas G Walker; Ann Marie Schmidt; Ottavio Arancio; Lih-Fen Lue; Shi Du Yan
Journal:  Curr Mol Med       Date:  2007-12       Impact factor: 2.222

Review 4.  Tau as a therapeutic target for Alzheimer's disease.

Authors:  A Boutajangout; E M Sigurdsson; P K Krishnamurthy
Journal:  Curr Alzheimer Res       Date:  2011-09       Impact factor: 3.498

5.  11C-PiB PET assessment of change in fibrillar amyloid-beta load in patients with Alzheimer's disease treated with bapineuzumab: a phase 2, double-blind, placebo-controlled, ascending-dose study.

Authors:  Juha O Rinne; David J Brooks; Martin N Rossor; Nick C Fox; Roger Bullock; William E Klunk; Chester A Mathis; Kaj Blennow; Jerome Barakos; Aren A Okello; Sofia Rodriguez Martinez de Liano; Enchi Liu; Martin Koller; Keith M Gregg; Dale Schenk; Ronald Black; Michael Grundman
Journal:  Lancet Neurol       Date:  2010-02-26       Impact factor: 44.182

6.  Proteolytic processing of the Alzheimer's disease amyloid precursor protein in brain and platelets.

Authors:  Geneviève Evin; Aiqin Zhu; R M Damian Holsinger; Colin L Masters; Qiao-Xin Li
Journal:  J Neurosci Res       Date:  2003-11-01       Impact factor: 4.164

7.  Ginkgo biloba for prevention of dementia: a randomized controlled trial.

Authors:  Steven T DeKosky; Jeff D Williamson; Annette L Fitzpatrick; Richard A Kronmal; Diane G Ives; Judith A Saxton; Oscar L Lopez; Gregory Burke; Michelle C Carlson; Linda P Fried; Lewis H Kuller; John A Robbins; Russell P Tracy; Nancy F Woolard; Leslie Dunn; Beth E Snitz; Richard L Nahin; Curt D Furberg
Journal:  JAMA       Date:  2008-11-19       Impact factor: 56.272

8.  Alzheimer disease in the US population: prevalence estimates using the 2000 census.

Authors:  Liesi E Hebert; Paul A Scherr; Julia L Bienias; David A Bennett; Denis A Evans
Journal:  Arch Neurol       Date:  2003-08

9.  Amyloid-related imaging abnormalities in patients with Alzheimer's disease treated with bapineuzumab: a retrospective analysis.

Authors:  Reisa Sperling; Stephen Salloway; David J Brooks; Donatella Tampieri; Jerome Barakos; Nick C Fox; Murray Raskind; Marwan Sabbagh; Lawrence S Honig; Anton P Porsteinsson; Ivan Lieberburg; H Michael Arrighi; Kristen A Morris; Yuan Lu; Enchi Liu; Keith M Gregg; H Robert Brashear; Gene G Kinney; Ronald Black; Michael Grundman
Journal:  Lancet Neurol       Date:  2012-02-03       Impact factor: 44.182

10.  Microglial scavenger receptors and their roles in the pathogenesis of Alzheimer's disease.

Authors:  Kim Wilkinson; Joseph El Khoury
Journal:  Int J Alzheimers Dis       Date:  2012-05-15
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  16 in total

Review 1.  Building a pipeline to discover and validate novel therapeutic targets and lead compounds for Alzheimer's disease.

Authors:  David A Bennett; Lei Yu; Philip L De Jager
Journal:  Biochem Pharmacol       Date:  2014-02-06       Impact factor: 5.858

2.  Why Drugs Fail in Late Stages of Development: Case Study Analyses from the Last Decade and Recommendations.

Authors:  Dolly A Parasrampuria; Leslie Z Benet; Amarnath Sharma
Journal:  AAPS J       Date:  2018-03-13       Impact factor: 4.009

Review 3.  Recent Advances in Microglia Modelling to Address Translational Outcomes in Neurodegenerative Diseases.

Authors:  Carla Cuní-López; Romal Stewart; Hazel Quek; Anthony R White
Journal:  Cells       Date:  2022-05-17       Impact factor: 7.666

Review 4.  The need for new approaches in CNS drug discovery: Why drugs have failed, and what can be done to improve outcomes.

Authors:  Valentin K Gribkoff; Leonard K Kaczmarek
Journal:  Neuropharmacology       Date:  2016-03-12       Impact factor: 5.250

5.  Effect of potent γ-secretase modulator in human neurons derived from multiple presenilin 1-induced pluripotent stem cell mutant carriers.

Authors:  Qing Liu; Shannon Waltz; Grace Woodruff; Joe Ouyang; Mason A Israel; Cheryl Herrera; Floyd Sarsoza; Rudolph E Tanzi; Edward H Koo; John M Ringman; Lawrence S B Goldstein; Steven L Wagner; Shauna H Yuan
Journal:  JAMA Neurol       Date:  2014-12       Impact factor: 18.302

6.  Pharmacophore modeling, in silico screening, molecular docking and molecular dynamics approaches for potential alpha-delta bungarotoxin-4 inhibitors discovery.

Authors:  R Barani Kumar; M Xavier Suresh; B Shanmuga Priya
Journal:  Pharmacogn Mag       Date:  2015-05       Impact factor: 1.085

7.  Eyes-closed task-free electroencephalography in clinical trials for Alzheimer's disease: an emerging method based upon brain dynamics.

Authors:  Elisabeth Cw van Straaten; Philip Scheltens; Alida A Gouw; Cornelis J Stam
Journal:  Alzheimers Res Ther       Date:  2014-12-19       Impact factor: 6.982

Review 8.  Tau Biology and Tau-Directed Therapies for Alzheimer's Disease.

Authors:  Lidia Bakota; Roland Brandt
Journal:  Drugs       Date:  2016-03       Impact factor: 9.546

9.  [18F]GE-180 PET Detects Reduced Microglia Activation After LM11A-31 Therapy in a Mouse Model of Alzheimer's Disease.

Authors:  Michelle L James; Nadia P Belichenko; Adam J Shuhendler; Aileen Hoehne; Lauren E Andrews; Christina Condon; Thuy-Vi V Nguyen; Vladimer Reiser; Paul Jones; William Trigg; Jianghong Rao; Sanjiv S Gambhir; Frank M Longo
Journal:  Theranostics       Date:  2017-03-24       Impact factor: 11.556

10.  Combining two repurposed drugs as a promising approach for Alzheimer's disease therapy.

Authors:  Ilya Chumakov; Serguei Nabirotchkin; Nathalie Cholet; Aude Milet; Aurélie Boucard; Damien Toulorge; Yannick Pereira; Esther Graudens; Sory Traoré; Julie Foucquier; Mickael Guedj; Emmanuel Vial; Noëlle Callizot; Rémy Steinschneider; Tangui Maurice; Viviane Bertrand; Catherine Scart-Grès; Rodolphe Hajj; Daniel Cohen
Journal:  Sci Rep       Date:  2015-01-08       Impact factor: 4.379

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