Skip to main content
SpringerLink
Log in

How can we recognize “disease modification” effects?

  • JNHA: Clinical Trials and Aging
  • Published:
JNHA - The Journal of Nutrition, Health and Aging

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  1. European Medicines Agency, Committee for Medicinal Products for Human Use. Guideline on medicinal products for the treatment of Alzheimer’s disease and other dementias. Doc. Ref. CPMP/EWP/553/95 Rev. 1. London. 24 July 2008.

  2. Mohs RC, Kawas C, Carillio M: Perspective: Optimal Design of Clinical Trials for Drugs Designed to Slow the Course of Alzheimer’s Disease. Alzheimer’s and Dementia 2006;2:131–139.

    Article  CAS  Google Scholar 

  3. Biomarkers Definitions Working Group, Atkinson AJ, Colburn WA, DeGruttola VG, DeMets DL, Downing GJ, Hoth DF, Oates JA, Peck CC, Schooley RT, Spilker BA, Woodcock J, Zeger SL. Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework. Clin Pharmacol Ther 2001;69:89–95.

    Article  Google Scholar 

  4. U.S. Department of Health and Human Services, Food and Drug Administration. Critical path opportunities report. Washington, DC, March 2006.

  5. Temple R. Are Surrogate Markers Adequate to Assess Cardiovascular Disease Drugs? JAMA 1999;282:790–795.

    Article  PubMed  CAS  Google Scholar 

  6. Matthews B, Siemers ER, Mozley PD. Imaging based measures of disease progression in clinical trials of disease modifying drugs for Alzheimer disease. Am J Geriatr Psychiatry 2003;11:146–159.

    PubMed  Google Scholar 

  7. Thal LJ, Kantarci K, Reiman EM, Klunk WE, Weiner MW, Zetterberg H, Galasko D, Praticò D, Griffin S, Schenk D, Siemers E. The Role of Biomarkers in Clinical Trials for Alzheimer’s Disease. Alzheimer Dis Assoc Disord 2006;20:6–15.

    Article  PubMed  Google Scholar 

  8. Frank RA, Galasko D, Hampel H, Hardy J, de Leon MJ, Mehta PD, Rogers J, Siemers E, Trojanowski JQ. Biological markers for therapeutic trials in Alzheimer’s disease. Proceedings of the biological markers working group; NIA initiative on neuroimaging in Alzheimer disease. Neurobiol Aging 2003;24:521–536.

    Article  PubMed  Google Scholar 

  9. Blennow K, Zetterberg H, Minthon L, Lannfelt L, Strid S, Annas P, Basun H, Andreasen N. Longitudinal stability of CSF biomarkers in Alzheimer’s disease. Neurosci Lett 2007;419:18–22.

    Article  PubMed  CAS  Google Scholar 

  10. Sunderland T, Wolozin B, Galasko D, Levy J, Dukoff R, Bahro M, Lasser R, Motter R, Lehtimäki T, Seubert P. Longitudinal stability of CSF tau levels in Alzheimer patients. Biol Psychiat 1999;46:750–755.

    Article  PubMed  CAS  Google Scholar 

  11. Andreasen N, Hesse C, Davidsson P, Minthon L, Wallin A, Winblad B, Vanderstichele H, Vanmechelen E, Blennow K. Cerebrospinal fluid beta-amyloid(1–42) in Alzheimer’s disease: differences between early- and late-onset Alzheimer’s disease and stability during the course of disease. Arch Neurol 1999;56:673–680.

    Article  PubMed  CAS  Google Scholar 

  12. Engler H, Forsberg A, Almkvist O, Blomquist G, Larsson E, Savitcheva I, Wall A, Ringheim A, Langstrom B, Nordberg A. Two-year follow-up of amyloid deposition in patients with Alzheimer’s disease. Brain 2006;129:2856–2866.

    Article  PubMed  Google Scholar 

  13. Tierney MC, Fisher RH, Lewis AJ, et al. The NINCDS-ADRDA Work Group criteria for the clinical diagnosis of probable Alzheimer’s disease: a clinicopathologic study of 57 cases. Neurology 1988;38:359–364.

    PubMed  CAS  Google Scholar 

  14. Siemers ER, Paul SM. Commentary on “A roadmap for the prevention of dementia: The inaugural Leon Thal Symposium”. Alzheimers Dement 2008;4:171–173.

    Article  PubMed  Google Scholar 

  15. Aizenstein HJ, Nebes RD, Saxton JA, Price JC, Mathis CA, Tsopelas ND, Ziolko SK, James JA, Snitz BE, Houck PR, Bi W, Cohen AD, Lopresti BJ, DeKosky ST, Halligan EM, Klunk WE. Frequent amyloid deposition without significant cognitive impairment among the elderly. Arch Neurol 2008;65:1509–1517.

    Article  PubMed  Google Scholar 

  16. Gilman S, Koller M, Black RS, Jenkins L, Griffith SG, Fox NC, Eisner L, Kirby L, Boada Rovira M, Forette F, Orgogozo JM for the AN1792(QS-21)-201 Study Team. Clinical effects of A immunization (AN1792) in patients with AD in an interrupted trial. Neurology 2005;64:1553–1562.

    Article  PubMed  CAS  Google Scholar 

  17. Fox NC, Black RS, Gilman S, Rossor MN, Griffith SG, Jenkins L, Koller M for the AN1792(QS-21)-201 Study Team. Effects of A immunization (AN1792) on MRI measures of cerbral volume in Alzheimer disease. Neurology 2005;64:1563–1572.

    Article  PubMed  CAS  Google Scholar 

  18. Siemers E, Skinner M, Dean RA, Gonzales C, Satterwhite J, Farlow M, Ness D, May PC. Safety, tolerability and changes in amyloid concentrations after administration of a -secretase inhibitor in volunteers. Clin Neuropharmacol 2005;28:126–132.

    Article  PubMed  CAS  Google Scholar 

  19. Siemers ER, Quinn JF, Kaye J, Farlow MR, Porsteinsson A, Tariot P, Zoulnouni P, Galvin JE, Holtzman DM, Knopman DS, Satterwhite J, Gonzales C, Dean RA, May PC. Effects of a -secretase inhibitor in a randomized study of patients with Alzheimer disease. Neurology 2006;66:602–604.

    Article  PubMed  CAS  Google Scholar 

  20. Siemers ER, Dean RA, Friedrich S, Ferguson-Sells L, Gonzales C, Farlow MR, May PC. Safety, tolerability and effects on plasma and cerebrospinal fluid amyloid-following inhibition of -secretase. Clin Neuropharmacol 2007;30:317–325.

    Article  PubMed  CAS  Google Scholar 

  21. Fleisher AS, Raman R, Siemers ER, Becerra L, Clark CM, Dean RA, Farlow MR, Galvin JE, Peskind ER, Quinn JF, Sherzai A, Sowell BB, Aisen PS, Thal LJ. Phase 2 safety trial targeting amyloid beta production with a gamma-secretase inhibitor in Alzheimer disease. Arch Neurol 2008;65:1031–1038.

    Article  PubMed  Google Scholar 

  22. Bateman RJ. A turnover in human subjects. Alzheimer’s and Dementia 2008;4(Suppl 2):T123.

    Article  Google Scholar 

  23. Siemers ER, Benson C, Gonzales C, Hansen R, Dean RA, Farlow M, DeMattos R. Safety assessments and biomarker changes following a monoclonal A antibody given to subjects with Alzheimer’s Disease. Alzheimer’s and Dementia 2006;2(Suppl):S80.

    Article  Google Scholar 

  24. Siemers ER, Friedrich S, Dean RA, Sethuraman G, Demattos RB, Jennings D, Tamagnan G, Marek K, Seibyl J. Safety, tolerability and biomarker effects of an A monoclonal antibody administered to patients with Alzheimer’s disease. Alzheimer’s and Dementia 2008;4(Suppl 2):T774.

    Article  Google Scholar 

  25. DeMattos RB, Dean RA, Friedrich S, Sethuraman G, Racke M, Karran EH, Paul SM, Siemers E. Alterations of novel A biomarkers after administration of a monoclonal antibody specific for soluble A. Hot topics presentation, International Conference on Alzheimer’s Disease, Chicago, IL, July 30, 2008.

  26. Grundman M, Black R. Clinical trials of bapineuzumab, a beta-amyloid-targeted immunotherapy in patients with mild to moderate Alzheimer’s disease. Alzheimer’s and Dementia 2008;4(Suppl 2):T166.

    Article  Google Scholar 

  27. Selkoe DJ. Alzheimer disease: mechanistic understanding predicts novel therapies. Ann Intern Med 2004;140:627–638.

    PubMed  CAS  Google Scholar 

  28. Hardy J. Selkoe DJ. The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 2002;297(5580):353–356.

    Article  PubMed  CAS  Google Scholar 

  29. Corder EH, Saunders AM, Strittmatter WJ, Schmechel D, Gaskell P, Small GW, Roses AD, Haines JL, Pericak-Vance MA (1993) Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science 261:921–923.

    Article  PubMed  CAS  Google Scholar 

  30. Saunders AM, Strittmatter WJ, Schmechel D, St. George-Hyslop PH, Pericak-Vance MA, Joo SH, Rosi BL, Gusella JF, Crapper-MacLachlan DR, Alberts MJ, Hulette C, Crain B, Goldgaber D, Roses AD. Association of apolipoprotein E allele 4 with late-onset familial and sporadic Alzheimer’s disease. Neurology 1993;43:1467–1472.

    PubMed  CAS  Google Scholar 

  31. Leber P. Guidelines for the clinical evaluation of anti-dementia drugs. First Draft. Rockville, MD: US Food and Drug Administration, 1990.

    Google Scholar 

  32. Thal LJ, Kantarci K, Reiman EM, Klunk WE, Weiner MW, Zetterberg H, Galasko D, Praticò D, Griffin S, Schenk D, Siemers E. The Role of Biomarkers in Clinical Trials for Alzheimer’s Disease. Alzheimer’s Dis Assoc Disord 2006;20:6–15.

    Article  Google Scholar 

  33. Sethuraman G, Siemers E, Tamura R, Offen W, Mohs R. The Design and Analysis of Alzheimer’s Disease Trials with a Delayed Start Period. International Society for Clinical Trials Management. Toronto, Canada, October 6, 2008.

Download references

Author information

Authors and Affiliations

  1. Alzheimer’s Disease Team, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA

    E. R. Siemers

Authors
  1. E. R. Siemers
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to E. R. Siemers.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Siemers, E.R. How can we recognize “disease modification” effects?. J Nutr Health Aging 13, 341–343 (2009). https://doi.org/10.1007/s12603-009-0036-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12603-009-0036-7

Keywords

Search

Navigation