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Clinical Trials of AD Delay of Onset: Enrichment by a Prognostic Genetic Biomarker

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Neurodegenerative Diseases: Integrative PPPM Approach as the Medicine of the Future

Part of the book series: Advances in Predictive, Preventive and Personalised Medicine ((APPPM,volume 2))

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Abstract

Modern medicine is shifting its focus to predictive and preventive healthcare utilization. To support this change, early intervention clinical trials that delay the onset of symptomatic disease must be conducted in a safe and cost-effective manner, and within a reasonable timeframe. Biomarkers in general, and pharmacogenetic determinants in particular, hold great promise for enabling the conduct of early intervention studies by allowing enrichment of the study population with high risk individuals while also minimizing participation of low risk subjects. In this chapter, we review one possible approach for the co-development of a therapeutic and companion prognostic. In the example cited, at the conclusion of the clinical trial, the biomarker will be evaluated for its utility in identifying individuals at risk of developing mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) in the next 5 years (i.e. prospective data will be generated to determine the biomarker’s qualification as a prognostic). Simultaneously, the therapeutic will be evaluated for its efficacy in delaying the onset of MCI due to AD in high risk subjects with normal cognition at study entry. This clinical trial in planning is projected to launch internationally in 2013. The strategic and operational aspects of this development program are expected to pave the way to the application of similar approaches for other early intervention indications, particularly within the context of neurodegenerative diseases.

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Authors and Affiliations

  1. IsraGene, Ltd., Rosh HaAyin, 48092, Israel

    Iris Grossman

  2. Duke University, 90344, Durham, NC, 27708-0120, USA

    Michael W. Lutz, Donna G. Crenshaw, Ann M. Saunders, Ornit Chiba-Falek & William K. Gottschalk

  3. Zinfandel Pharmaceuticals Inc., 110395, Research Triangle Park, Chapel Hill, NC, 27709, USA

    Allen D. Roses

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  1. Iris Grossman
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    Silvia Mandel

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Grossman, I. et al. (2013). Clinical Trials of AD Delay of Onset: Enrichment by a Prognostic Genetic Biomarker. In: Mandel, S. (eds) Neurodegenerative Diseases: Integrative PPPM Approach as the Medicine of the Future. Advances in Predictive, Preventive and Personalised Medicine, vol 2. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5866-7_7

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