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Translation of Pre-Clinical Studies into Successful Clinical Trials for Alzheimer's Disease: What are the Roadblocks and How Can They Be Overcome?

Lookup NU author(s): Dr Elizabeta Mukaetova-Ladinska, Dr Masafumi Ihara, Professor Raj KalariaORCiD

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Abstract

Preclinical studies are essential for translation to disease treatments and effective use in clinical practice. An undue emphasis on single approaches to Alzheimer's disease (AD) appears to have retarded the pace of translation in the field, and there is much frustration in the public about the lack of an effective treatment. We critically reviewed past literature (1990-2014), analyzed numerous data, and discussed key issues at a consensus conference on Brain Ageing and Dementia to identify and overcome roadblocks in studies intended for translation. We highlight various factors that influence the translation of preclinical research and highlight specific preclinical strategies that have failed to demonstrate efficacy in clinical trials. The field has been hindered by the domination of the amyloid hypothesis in AD pathogenesis while the causative pathways in disease pathology are widely considered to be multifactorial. Understanding the causative events and mechanisms in the pathogenesis are equally important for translation. Greater efforts are necessary to fill in the gaps and overcome a variety of confounds in the generation, study design, testing, and evaluation of animal models and the application to future novel anti-dementia drug trials. A greater variety of potential disease mechanisms must be entertained to enhance progress.

Publication metadata

Author(s): Banik A, Brown RE, Bamburg J, Lahiri DK, Khurana D, Friedland RP, Chen W, Ding Y, Mudher A, Padjen AL, Mukaetova-Ladinska E, Ihara M, Srivastava S, Srivastava MVP, Masters CL, Kalaria RN, Anand A

Publication type: Review

Publication status: Published

Journal: Journal of Alzheimer's Disease

Year: 2015

Volume: 47

Issue: 4

Pages: 815-843

Online publication date: 11/08/2015

Acceptance date: 21/05/2015

ISSN (print): 1387-2877

ISSN (electronic): 1875-8908

Publisher: IOS PRESS

URL: http://dx.doi.org/10.3233/JAD-150136

DOI: 10.3233/JAD-150136

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