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Developing new treatments for Alzheimer's disease: the who, what, when, and how of biomarker-guided therapies

Published online by Cambridge University Press:  23 May 2008

Constantine G. Lyketsos ,
Christine A. Szekely ,
Michelle M. Mielke ,
Paul B. Rosenberg  and
Peter P. Zandi
Constantine G. Lyketsos*
Affiliation:
Johns Hopkins Bayview, Department of Psychiatry and Behavioral Sciences, School of Medicine, and Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, U.S.A.
Christine A. Szekely
Affiliation:
Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University and Samuel Oschin Comprehensive Cancer Center, Cedars Sinai Medical Center, Los Angeles, California, U.S.A.
Michelle M. Mielke
Affiliation:
Department of Psychiatry, Johns Hopkins Bayview and Johns Hopkins University, Baltimore, Maryland, U.S.A.
Paul B. Rosenberg
Affiliation:
Department of Psychiatry, Johns Hopkins Bayview and Johns Hopkins University, Baltimore, Maryland, U.S.A.
Peter P. Zandi
Affiliation:
Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, U.S.A.
*
Correspondence should be addressed to: Constantine G. Lyketsos, MD, MHS, The Elizabeth Plank Althouse Professor, Chair, Department of Psychiatry, Johns Hopkins Bayview, 5300 Alpha Commons Drive, 4th floor, Baltimore, Maryland, 21224, U.S.A. Phone: +1 410 550 0062; Fax: +1 410 550 1407. Email: kostas@jhmi.edu.
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Abstract

This synthetic review presents an approach to the use of biomarkers for the development of new treatments for Alzheimer's disease (AD). After reviewing the process of translation as applied to AD, the paper provides a general update on what is known about the biology of the disease, and highlights currently available treatments. This is followed by a discussion of future drug development for AD emphasizing the roles that biomarkers are likely to play in this process: (1) define patients who are going to progress rapidly for the purpose of trial enrichment; (2) differentiate disease and therapeutically relevant AD subtypes; (3) assess the potential activity of specific therapies in vivo or ex vivo; and (4) measure the underlying disease state, so as to (a) detect disease and assess drug response in asymptomatic patients, (b) serve as a secondary outcome measure in clinical trials of symptomatic patients, and (c) decide if further development of a treatment should be stopped if not likely to be effective. Several examples are used to illustrate each biomarker utility in the AD context.

Type
Review Article
Information
International Psychogeriatrics , Volume 20 , Issue 5 , October 2008 , pp. 871 - 889
Copyright
Copyright © International Psychogeriatric Association 2008

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