Developing new treatments for Alzheimer's disease: the who, what, when, and how of biomarker-guided therapies.
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.
Lyketsos
Constantine G
CG
Department of Psychiatry and Behavioral Sciences, School of Medicine, Johns Hopkins University, Baltimore, Maryland, U.S.A. kostas@jhmi.edu
Szekely
Christine A
CA
Mielke
Michelle M
MM
Rosenberg
Paul B
PB
Zandi
Peter P
PP
D000544:Alzheimer Disease / Q000175:diagnosis / Q000473:pathology / Q000628:therapy*; D000814:Aniline Compounds; D015415:Biomarkers / Q000032:analysis*; D054316:Biomarkers, Pharmacological / Q000032:analysis; D001921:Brain / Q000473:pathology; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003072:Cognition Disorders / Q000175:diagnosis / Q000473:pathology / Q000628:therapy; D018450:Disease Progression; D015195:Drug Design; D006801:Humans; D009483:Neuropsychological Tests; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging / Q000473:pathology; D049268:Positron-Emission Tomography / Q000379:methods; D011619:Psychotropic Drugs / Q000627:therapeutic use; D011869:Radioligand Assay; D013844:Thiazoles
C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000814:Aniline Compounds; D015415:Biomarkers; D054316:Biomarkers, Pharmacological; D002800:Cholinesterase Inhibitors; D011619:Psychotropic Drugs; D013844:Thiazoles