Translation of pre-clinical studies into successful clinical trials for Alzheimer's disease: What are the roadblocks and how can they be overcome?

Avijit Banik, Richard E. Brown, James Bamburg, Debomoy K. Lahiri, Dheeraj Khurana, Robert P. Friedland, Wei Chen, Ying Ding, Amritpal Mudher, Ante L. Padjen, Elizabeta Mukaetova-Ladinska, Masafumi Ihara, Sudhir Srivastava, M. V.Padma Srivastava, Colin L. Masters, Raj N. Kalaria, Akshay Anand

Research output: Contribution to journalReview article

22 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)815-843
Number of pages29
JournalJournal of Alzheimer's Disease
Volume47
Issue number4
DOIs
StatePublished - Aug 11 2015

    Fingerprint

Keywords

  • Alzheimer's disease
  • Animal model
  • Dementia
  • Memory disorder
  • Pre-clinical
  • Treatment

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Clinical Psychology

Cite this

Banik, A., Brown, R. E., Bamburg, J., Lahiri, D. K., Khurana, D., Friedland, R. P., Chen, W., Ding, Y., Mudher, A., Padjen, A. L., Mukaetova-Ladinska, E., Ihara, M., Srivastava, S., Srivastava, M. V. P., Masters, C. L., Kalaria, R. N., & Anand, A. (2015). Translation of pre-clinical studies into successful clinical trials for Alzheimer's disease: What are the roadblocks and how can they be overcome? Journal of Alzheimer's Disease, 47(4), 815-843. https://doi.org/10.3233/JAD-150136