Alzheimer's Therapeutics: Translation of Preclinical Science to Clinical Drug Development
| Autor: | Phil C. Wong, Tatiana Melnikova, Alena Savonenko, Juan C. Troncoso, Paul F. Worley, Donald L. Price, Tong Li, Andrew Hiatt |
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| Rok vydání: | 2011 |
| Předmět: |
Pharmacology
Predictive validity medicine.medical_specialty Mechanism (biology) business.industry Drug Evaluation Preclinical Disease medicine.disease Translational Research Biomedical Clinical trial Efficacy Disease Models Animal Psychiatry and Mental health Drug development Alzheimer Disease Drug Design Neuropsychopharmacology Reviews medicine Animals Humans Amyloid cascade Alzheimer's disease Intensive care medicine business Neuroscience |
| Zdroj: | Neuropsychopharmacology. 37:261-277 |
| ISSN: | 1740-634X 0893-133X |
| DOI: | 10.1038/npp.2011.211 |
| Popis: | Over the past three decades, significant progress has been made in understanding the neurobiology of Alzheimer's disease. In recent years, the first attempts to implement novel mechanism-based treatments brought rather disappointing results, with low, if any, drug efficacy and significant side effects. A discrepancy between our expectations based on preclinical models and the results of clinical trials calls for a revision of our theoretical views and questions every stage of translation—from how we model the disease to how we run clinical trials. In the following sections, we will use some specific examples of the therapeutics from acetylcholinesterase inhibitors to recent anti-Aβ immunization and γ-secretase inhibition to discuss whether preclinical studies could predict the limitations in efficacy and side effects that we were so disappointed to observe in recent clinical trials. We discuss ways to improve both the predictive validity of mouse models and the translation of knowledge between preclinical and clinical stages of drug development. |
| Databáze: | OpenAIRE |
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