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

Alzheimer's and Dementia

Volumn 9, Issue 1, 2013, Pages 50-57

  Becker, Robert E ^a   Greig, Nigel H ^b  

^a Aristea Translational Medicine Corp   (United States)

^b NATIONAL INSTITUTE ON AGING   (United States)

Author keywords

( ) Phenserine; AD drug development; Scientific practices; Validity

Indexed keywords

PHENSERINE;

ALZHEIMER DISEASE; CLINICAL TRIAL (TOPIC); DRUG EFFICACY; DRUG ELIMINATION; DRUG HALF LIFE; DRUG TISSUE LEVEL; HUMAN; NEUROSCIENCE; NONHUMAN; PRIORITY JOURNAL; REVIEW; SYSTEMATIC ERROR; TRAUMATIC BRAIN INJURY; VASCULAR AMYLOIDOSIS;

EID: 84872106221     PISSN: 15525260     EISSN: 15525279     Source Type: Journal    
DOI: 10.1016/j.jalz.2012.01.007     Document Type: Article

References (56)

1. M.D. Lindner, R.A. McArthur, S.A. Deadwyler, R.E. Hampson, and P.N. Tariot Development, optimization and use of preclinical behavioral models to maximize the productivity of drug discovery for Alzheimer's disease R.A. McArthur, F. Borsini, Animal and Translational Models for CNS Drug Discovery: Neurological Disorders 2008 Academic Press San Diego, CA 93 157
2. R.E. Becker, and N.H. Greig Alzheimer's disease drug development in 2008 and beyond: problems and opportunities Curr Alzheimer Res 5 2008 347 357
3. R.E. Becker, and N.H. Greig Alzheimer's disease drug development: old problems require new priorities CNS Neurol Disord Drug Targets 7 2008 499 511
4. R.E. Becker, N.H. Greig, and E. Giacobini Why do so many drugs for Alzheimer's disease fail in development? Time for new methods and new practices? J Alzheimers Dis 15 2008 303 325
5. R.E. Becker, and N.H. Greig Neuropsychiatric clinical trials: should they accommodate to "Real-World" practices or set standards for clinical practices? J Clin Psychopharmacol 29 2009 56 64
6. R.E. Becker, L.K. Unni, and N.H. Greig Resurrecting clinical pharmacology as a context for Alzheimer disease drug development Curr Alzheimer Res 6 2009 79 81
7. R.E. Becker, and N.H. Greig Why so few drugs for Alzheimer's disease? Are methods failing drugs? Curr Alzheimer Res 7 2010 642 651
8. R.E. Becker, and N.H. Greig Lost in translation: neuropsychiatric drug development Sci Transl Med 2 61 2010 61rv6
9. L.S. Schneider, and D.K. Lahiri The perils of Alzheimer's drug development Curr Alzheimer Res 6 2009 77 79
10. S.J. Enna, and M. Williams Challenges in the search for drugs to treat central nervous system disorders J Pharmacol Exp Ther 329 2009 404 411
11. N. Engelhardt, A.D. Feiger, K.O. Cogger, D. Sikich, D.J. DeBrota, and J.D. Lipsitz Rating the raters: assessing the quality of Hamilton rating scale for depression clinical interviews in two industry sponsored clinical drug trials J Clin Psychopharmacol 26 2006 71 74
12. K.A. Kobak, J.D. Lipsitz, J.B. Williams, N. Engelhardt, and K.M. Bellew A new approach to rater training and certification in a multicenter clinical trial J Clin Psychopharmacol 25 2005 407 412
13. Kobak KA, DeBrota DJ, Engelhardt N, Williams JB. Site vs. centralized raters in a clinical depression trial. Paper presented at: The 46th Annual Meeting of the National Institute of Mental Health, New Clinical Drug Evaluation Unit; 2006; Boca Raton, FL.
14. N.H. Greig, K. Sambarmurti, Q.S. Yu, A. Brossi, G. Brunsma, and D.K. Lahiri An overview of phenserine tartrate, a novel acetylcholinesterase inhibitor for the treatment of Alzheimer's disease Curr Alzheimer Res 2 2005 281 290
15. K.T. Shaw, T. Utsuki, J. Rogers, Q.S. Yu, K. Sambamurti, A. Brossi, Y.W. Ge, D.K. Lahiri, and N.H. Greig Phenserine regulates translation of beta -amyloid precursor protein mRNA by a putative interleukin-1 responsive element, a target for drug development Proc Natl Acad Sci USA 98 2001 7605 7610
16. D.K. Lahiri, D. Chen, D. Vivien, Y.W. Ge, N.H. Greig, and J.T. Rogers Role of cytokines in the gene expression of amyloid beta-protein precursor: identification of a 5'-UTR-binding nuclear factor and its implications in Alzheimer's disease J Alzheimers Dis 5 2003 81 90
17. D.K. Lahiri, D. Chen, B. Maloney, H.W. Holloway, Q.S. Yu, T. Utsuki, T. Giordano, K. Sambamurti, and N.H. Greig The experimental Alzheimer's disease drug posiphen [(+)-phenserine] lowers amyloid-beta peptide levels in cell culture and mice J Pharmacol Exp Ther 320 2007 386 396
18. K. Sambamurti, A. Prakasam, S. Anitha, C. Venugopa, E. Cullen, and Y. Zhou Oral phenserine tartrate treatment is associated with reduced plasma Aβ 1-42 in a phase I clinical study K. Khalid Iqbal, B. Winblad, J. Avila, Alzheimer's Disease New Advances 2007 Medimond Bologna, Italy 571 575
19. N.H. Greig, J. Ruckle, P. Comer, L. Brownell, H.W. Holloway, D.R. Flanagan Jr., C.J. Canfield, and R.G. Burford Anticholinesterase and pharmacokinetic profile of phenserine in healthy elderly human subjects Curr Alzheimer Res 2 2005 483 492
20. R.E. Becker Lessons from Darwin: 21st century designs for clinical trials Curr Alzheimer Res 4 2007 458 467
21. R.E. Becker, and S. Markwell Problems arising from the generalizing of treatment efficacy from clinical trials in Alzheimer's disease Clin Drug Invest 19 2000 33 41
22. A. Markou, C. Chiamulera, M.A. Geyer, M. Tricklebank, and T. Steckler Removing obstacles in neuroscience drug discovery: the future path for animal models Neuropsychopharmacology 34 2009 74 89
23. M.N. Pangalos, L.E. Schechter, and O. Hurko Drug development for CNS disorders: strategies for balancing risk and reducing attrition Nat Rev Drug Discov 6 2007 521 532
24. A.W. Chan, A. Hróbjartsson, K.J. Jørgensen, P.C. Gøtzsche, and D.G. Altman Discrepancies in sample size calculations and data analyses reported in randomised trials: comparison of publications with protocols BMJ 337 2008 a2299
25. I. Boutron, S. Dutton, P. Ravaud, and D.G. Altman Reporting and interpretation of randomized controlled trials with statistically nonsignificant results for primary outcomes JAMA 303 2010 2058 2064
26. M.O. Baerlocher, J.O. Brien, M. Newton, T. Gautam, and J. Noble Data integrity, reliability and fraud in medical research Eur J Intern Med 21 2010 40 45
27. K.O. Cogger Rating rater improvement: a method for estimating increased effect size and reduction of clinical trial costs J Clin Psychopharmacol 27 2007 418 420
28. M.A. Demitrack, D. Faries, J.M. Herrera, D. DeBrota, and W.Z. Potter The problem of measurement error in multisite clinical trials Psychopharmacol Bull 34 1998 19 24
29. R.E. Becker, and N.H. Greig Threats to irreproducibility from an epidemic of reproducible irreproducible results J Irreproducible Results 51 2010 10 13
30. K.I. Kaitin Deconstructing the drug development process: the new face of innovation Clin Pharmacol Ther 87 2010 856-1
31. P.T. Lansbury Jr. Back to the future: the 'old fashioned' way to new medications for neurodegenerations Nat Rev Neurosci 5 2004 S51 S57
32. S.M. Paul, D.S. Mytelka, C.T. Dunwiddle, C.C. Persinger, B.H. Numos, S.R. Lindborg, and A.L. Schacht How to improve R&D productivity: the pharmaceutical industry's grand challenge Nat Rev Drug Discov 9 2010 203 214
33. D.F. Klein The loss of serendipity in psychopharmacology JAMA 299 2008 1063 1065
34. P.S. Aisen, S. Andrieu, C. Sampaio, M. Carrillo, Z.S. Khachaturian, and B. Dubios Report of the task force on designing clinical trials in early (preclinical) dementia Neurology 76 2011 280 286
35. R. Craven The risky business of drug development in neurology Neurology 10 2011 116 117
36. S.J. Enna, and M. Williams Challenges in the search for drugs to treat central nervous system disorders J Pharmacol Exp Ther 329 2009 404 411
37. Weiner M. Alzheimer's disease neuroimaging initiative. Available at: http://www.adni-info.org/Scientists/Pdfs/Grant-new.pdf. Accessed June 10, 2011.
38. E.H. Turner, A.M. Matthews, E. Linardatos, R.A. Tell, and R. Rosenthal Selective publication of antidepressant trials and its influence on apparent efficacy N Engl J Med 358 2008 252 260
39. E.S. Sena, H.B. van der Worp, P.M. Bath, D.W. Howells, and M.R. Macleod Publication bias in reports of animal stroke studies leads to major overstatement of efficacy PLoS Biol 8 2010 e1000344
40. I. Chalmers Underreporting research is scientific misconduct JAMA 9 1990 1405 1408
41. A. Kadir, N. Andreasen, O. Almkvist, A. Wall, A. Forsberg, and H. Engler Effect of phenserine treatment on brain functional activity and amyloid in Alzheimer's disease Ann Neurol 63 2008 621 631
42. B. Winblad, E. Giacobini, L. Frölich, L.T. Friedhoff, G. Bruinsma, R.E. Becker, and N.H. Greig Phenserine efficacy in Alzheimer's disease J Alzheimers Dis 22 2010 1201 1208
43. Mismanaged measures [editorial] Nature 452 2008 504
44. L.S. Schneider, and M. Sano Current Alzheimer's disease clinical trials: methods and placebo outcomes Alzheimers Dement 5 2009 388 397
45. M. Folstein, S. Folstein, and P. Mc Hugh Mini mental state: a practical method for grading the cognitive state of patients for the clinician J Psychiatr Res 12 1975 189 198
46. W.G. Rosen, R.G. Mohs, and K.L. Davis A new rating scale for Alzheimer's disease Am J Psychiatry 141 1984 1356 1364
47. J.T. Rogers, L.M. Leiter, J. McPhee, C.M. Cahill, S.S. Zhan, H. Potter, and L.N. Nilsson Translation of the Alzheimer amyloid precursor protein mRNA is up-regulated by interleukin-1 through 5'-untranslated region sequences J Biol Chem 274 1999 6421 6431
48. R.C. Mohs, W.G. Rosen, and K.L. Davis The Alzheimer's disease assessment scale: an instrument for assessing treatment efficacy Psychopharmacol Bull 19 1983 448 450
49. D. Galasko, D. Bennett, M. Sano, E. Ernesto, R. Thomas, M. Grundman, and S. Ferris An inventory to assess activities of daily living for clinical trials in Alzheimer's disease. The Alzheimer's disease cooperative study Alzheimer Dis Assoc Disord 11 1997 S33 S39
50. F. Leger, P.O. Ferragut, N.G. Caron, S. Losoni, C. Vital, F. Tison, E. Bezard, and A. Vitut Protein Aggregation in the aging retina J Neuropathol Exp Neurol 70 2011 63 68
51. T. Dentchev, A.H. Milan, V.M. Lee, J.Q. Trojanowski, and J.L. Dunaief Amyloid-beta is found in drusen from some age-related macular degeneration retinas, but not in drugsen from normal retinas Mol Vis 14 2003 184 190
52. H.G. Blaauwgeers, G.M. Holtkamp, H. Rutten, A.N. Witmer, P. Koolwijk, and T.A. Partanen Polarized vascular endothelial growth factor secretion by human retinal pigment epithelium and localization of vascular endothelial growth factor receptors on the inner choriocapillaris. Evidence for a trophic paracrine relation Am J Pathol 155 1999 421 428
53. G. Katz, L. Giavedoni, R. Muni, T. Evans, M. Pezda, and D. Wong Effectiveness at 1 year of monthly versus variable-dosing Intravitreal Ranibizumab in the treatment of choroidal neovascularization secondary to age-related macular degeneration Retina 32 2012 293 298
54. T.A. Kokjohn, G.D. Van Vickle, C.L. Maarouf, W.M. Kalback, J.M. Hunter, and I.D. Daugs Chemical characterization of pro-inflammatory amyloid-beta peptides in human atherosclerotic lesions and platelets Biochim Biophys Acta 1812 2011 1508 1514
55. P. Duhem The aim and structure of physical science 1991 Princeton University Press Princeton, NJ
56. Pondrom S. Alzheimer's research consortium receives $54 million. Available at: http://ucsdnews.ucsd.edu/newsrel/health/ADCS%20NRa.htm. Accessed June 10, 2011.