Translational medicine perspective in development of disease modifying therapies for Alzheimer's disease: biomarkers to buy down the risk

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most common cause of age-related dementia. Currently available pharmacologic therapies, including acetylcholinesterase (AChE) inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists, only treat symptoms and do not address the underlying neurodegeneration. In addition to potentially improve the accuracy of diagnosis, biomarkers serve important roles for the development of putative disease-modifying drugs for AD. In this article, we review the existing and emerging areas of biomarker research and development for AD. Biochemical biomarkers in cerebrospinal fluid have been used to provide a link to disease pathology and may provide important proof of concept data for several classes of emerging therapeutics. Imaging biomarkers including volumetric magnetic resonance imaging and positron emission tomography assessing either glucose utilization or radioligands binding to amyloid plaque are discussed. Appropriate uses of these biomarkers in the context of the development of disease-modifying therapies are discussed. Drug Dev Res 70 : 60-69, 2009.

“Hot Spots” in Medicinal Chemistry

“…Studies directed to define critical biomarkers that could assist in monitoring clinical trials and decrease the risk of lengthy and eventually unfruitful studies have been reviewed. [67] This is a very promising indication toward a more efficient and successful approach in the future, enabling the discovery and development of drugs that should ultimately be preventive and/or curative for patients suffering from Alzheimer's and Parkinson's diseases. …”