Abstract
Alzheimer’s disease (AD)—a complex disease showing multiple pathomechanistic alterations—is triggered by nonlinear dynamic interactions of genetic/epigenetic and environmental risk factors, which, ultimately, converge into a biologically heterogeneous disease. To tackle the burden of AD during early preclinical stages, accessible blood-based biomarkers are currently being developed. Specifically, next-generation clinical trials are expected to integrate positive and negative predictive blood-based biomarkers into study designs to evaluate, at the individual level, target druggability and potential drug resistance mechanisms. In this scenario, systems biology holds promise to accelerate validation and qualification for clinical trial contexts of use—including proof-of-mechanism, patient selection, assessment of treatment efficacy and safety rates, and prognostic evaluation. Albeit in their infancy, systems biology-based approaches are poised to identify relevant AD “signatures” through multifactorial and interindividual variability, allowing us to decipher disease pathophysiology and etiology.
disease-modifying drugs.
| Original language | English |
|---|---|
| Pages (from-to) | 177-191 |
| Number of pages | 15 |
| Journal | Dialogues in Clinical Neuroscience |
| Volume | 21 |
| Issue number | 2 |
| DOIs | |
| State | Published - 2019 |
Keywords
- Alzheimer’s disease
- Biomarker-drug codevelopment
- Blood-based biomarker
- Clinical trial
- Context of use
- Pathophysiology
- Precision medicine
- Predictive biomarker
- Systems biology
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Blood-based systems biology biomarkers for next-generation clinical trials in Alzheimer’s disease. / Alzheimer Precision Medicine Initiative (APMI).
In: Dialogues in Clinical Neuroscience, Vol. 21, No. 2, 2019, p. 177-191.Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Blood-based systems biology biomarkers for next-generation clinical trials in Alzheimer’s disease
AU - Alzheimer Precision Medicine Initiative (APMI)
AU - Hampel, Harald
AU - Vergallo, Andrea
AU - Afshar, Mohammad
AU - Akman-Anderson, Leyla
AU - Arenas, Joaquín
AU - Benda, Norbert
AU - Batrla, Richard
AU - Broich, Karl
AU - Caraci, Filippo
AU - Cuello, A. Claudio
AU - Emanuele, Enzo
AU - Haberkamp, Marion
AU - Kiddle, Steven J.
AU - Lucía, Alejandro
AU - Mapstone, Mark
AU - Verdooner, Steven R.
AU - Woodcock, Janet
AU - Lista, Simone
AU - Aguilar, Lisi Flores
AU - Babiloni, Claudio
AU - Baldacci, Filippo
AU - Black, Keith L.
AU - Bokde, Arun L.W.
AU - Bonuccelli, Ubaldo
AU - Cacciola, Francesco
AU - Castrillo, Juan
AU - Cavedo, Enrica
AU - Ceravolo, Roberto
AU - Chiesa, Patrizia A.
AU - Corvol, Jean Christophe
AU - Cummings, Jeffrey L.
AU - Depypere, Herman
AU - Dubois, Bruno
AU - Duggento, Andrea
AU - Escott-Price, Valentina
AU - Federoff, Howard
AU - Ferretti, Maria Teresa
AU - Fiandaca, Massimo
AU - Frank, Richard A.
AU - Garaci, Francesco
AU - Geerts, Hugo
AU - Giorgi, Filippo S.
AU - Goetzl, Edward J.
AU - Graziani, Manuela
AU - Habert, Marie Odile
AU - Herholz, Karl
AU - Kapogiannis, Dimitrios
AU - Karran, Eric
AU - Kim, Seung H.
AU - O’bryant, Sid E.
N1 - Funding Information: This research benefited from the support of the Program “PHOENIX” led by the Sorbonne University Foundation and sponsored by la Fondation pour la Recherche sur Alzheimer. HH is supported by the AXA Research Fund, the “Fondation partenariale Sorbonne Université,” and the “Fondation pour la Recherche sur Alzheimer,” Paris, France. The research leading to these results has received funding from the program “Investissements d’avenir” ANR-10-IAIHU-06 (Agence Nationale de la Recherche-10-IA Agence Institut Hospitalo-Universitaire-6). SJK is supported by a MRC Career Development Award (MR/P021573/1). HH serves as Senior Associate Editor for the Journal Alzheimer’s & Dementia; he received lecture fees from Biogen and Roche, research grants from Pfizer, Avid, and MSD Avenir (paid to the institution), travel funding from Functional Neuromodulation, Axovant, Eli Lilly, and company, Takeda and Zinfandel, GE-Healthcare, and Oryzon Genomics, consultancy fees from Qynapse, Jung Diagnostics, Cytox Ltd., Axovant, Anavex, Takeda, and Zinfandel, GE Healthcare, Oryzon Genomics, and Functional Neuromodulation, and participated in scientific advisory boards of Functional Neuromodulation, Axovant, Eisai, Eli Lilly and company, Cytox Ltd., GE Healthcare, Takeda, and Zinfandel, Oryzon Genomics and Roche Diagnostics. MA is employee and shareholder of Ariana Pharma. RB is an employee of Roche Diagnostics. SJK received an honorarium for serving on an advisory board of Roche Diagnostics. MM has patents pending to Georgetown University. The terms of this arrangement have been reviewed and approved by the University of California, Irvine, in accordance with its conflict of interest policies. SL received lecture honoraria from Roche. Funding Information: Alzheimer Precision Medicine Initiative – Working Group (APMI–WG): Mohammad Afshar (Paris), Lisi Flores Aguilar (Montréal), Leyla Akman-Anderson (Sacramento), Joaquín Arenas (Madrid), Richard Batrla (Rotkreuz), Claudio Babiloni (Rome), Filippo Baldacci (Pisa), Norbert Benda (Bonn), Keith L. Black (Los Angeles), Arun L.W. Bokde (Dublin), Ubaldo Bonuccelli (Pisa), Karl Broich (Bonn), Francesco Cacciola (Siena), Filippo Caraci (Catania), Juan Castrillo† (Derio), Enrica Cavedo (Paris), Roberto Ceravolo (Pisa), Patrizia A. Chiesa (Paris), Jean-Christophe Corvol (Paris), Augusto Claudio Cuello (Montréal), Jeffrey L. Cummings (Las Vegas), Herman Depypere (Gent), Bruno Dubois (Paris), Andrea Duggento (Rome), Enzo Emanuele (Robbio), Valentina Escott-Price (Cardiff), Howard Federoff (Irvine), Maria Teresa Ferretti (Zürich), Massimo Fiandaca (Irvine), Richard A. Frank (Malvern), Francesco Garaci (Rome), Hugo Geerts (Berwyn), Filippo S. Giorgi (Pisa), Edward J. Goetzl (San Francisco), Manuela Graziani (Roma), Marion Haber-kamp (Bonn), Marie-Odile Habert (Paris), Harald Hampel (Paris), Karl Herholz (Manchester), Dimitrios Kapogiannis (Baltimore), Eric Karran (Cambridge), Steven J. Kiddle (Cambridge), Seung H. Kim (Seoul), Yosef Koronyo (Los Angeles), Maya Koronyo-Hamaoui (Los Angeles), Todd Langevin (Minneapolis-Saint Paul), Stéphane Lehéricy (Paris), Alejandro Lucía (Madrid), Simone Lista (Paris), Jean Lorenceau (Paris), Dalila Mango (Rome), Mark Mapstone (Irvine), Christian Neri (Paris), Robert Nisticò (Rome), Sid E. O’bryant (Fort Worth), Giovanni Palermo (Pisa), George Perry (San Antonio), Craig Ritchie (Edinburgh), Simone Rossi (Siena), Amira Saidi (Rome), Emiliano Santarnecchi (Siena), Lon S. Schneider (Los Angeles), Olaf Sporns (Bloomington), Nicola Toschi (Rome), Steven R. Verdooner (Sacramento), Andrea Vergallo (Paris), Nicolas Villain (Paris), Lindsay A. Welikovitch (Montréal), Janet Woodcock (Silver Spring), Erfan Younesi (Esch-sur-Alzette). This research benefited from the support of the Program “PHOENIX” led by the Sorbonne University Foundation and sponsored by la Fondation pour la Recherche sur Alzheimer. HH is supported by the AXA Research Fund, the “Fonda-tion partenariale Sorbonne Université,” and the “Fonda-tion pour la Recherche sur Alzheimer,” Paris, France. The research leading to these results has received funding from the program “Investissements d’avenir” ANR-10-IAIHU-06 (Agence Nationale de la Recherche-10-IA Agence Institut Hospitalo-Universitaire-6). SJK is supported by a MRC Career Development Award (MR/P021573/1). HH serves as Senior Associate Editor for the Journal Alzheimer’s & Dementia; he received lecture fees from Biogen and Roche, research grants from Pfizer, Avid, and MSD Avenir (paid to the institution), travel funding from Functional Neuro-modulation, Axovant, Eli Lilly, and company, Takeda and Zinfandel, GE-Healthcare, and Oryzon Genomics, consultancy fees from Qynapse, Jung Diagnostics, Cytox Ltd., Axovant, Anavex, Takeda, and Zinfandel, GE Healthcare, Oryzon Genomics, and Functional Neuromodulation, and participated in scientific advisory boards of Functional Neuromodulation, Axovant, Eisai, Eli Lilly and company, Cytox Ltd., GE Healthcare, Takeda, and Zinfandel, Oryzon Genomics and Roche Diagnostics. MA is employee and shareholder of Ariana Pharma. RB is an employee of Roche Diagnostics. SJK received an honorarium for serving on an advisory board of Roche Diagnostics. MM has patents pending to Georgetown University. The terms of this arrangement have been reviewed and approved by the University of California, Irvine, in accordance with its conflict of interest policies. SL received lecture honoraria from Roche. Publisher Copyright: © 2019, AICH – Servier Group
PY - 2019
Y1 - 2019
N2 - Alzheimer’s disease (AD)—a complex disease showing multiple pathomechanistic alterations—is triggered by nonlinear dynamic interactions of genetic/epigenetic and environmental risk factors, which, ultimately, converge into a biologically heterogeneous disease. To tackle the burden of AD during early preclinical stages, accessible blood-based biomarkers are currently being developed. Specifically, next-generation clinical trials are expected to integrate positive and negative predictive blood-based biomarkers into study designs to evaluate, at the individual level, target druggability and potential drug resistance mechanisms. In this scenario, systems biology holds promise to accelerate validation and qualification for clinical trial contexts of use—including proof-of-mechanism, patient selection, assessment of treatment efficacy and safety rates, and prognostic evaluation. Albeit in their infancy, systems biology-based approaches are poised to identify relevant AD “signatures” through multifactorial and interindividual variability, allowing us to decipher disease pathophysiology and etiology.disease-modifying drugs.
AB - Alzheimer’s disease (AD)—a complex disease showing multiple pathomechanistic alterations—is triggered by nonlinear dynamic interactions of genetic/epigenetic and environmental risk factors, which, ultimately, converge into a biologically heterogeneous disease. To tackle the burden of AD during early preclinical stages, accessible blood-based biomarkers are currently being developed. Specifically, next-generation clinical trials are expected to integrate positive and negative predictive blood-based biomarkers into study designs to evaluate, at the individual level, target druggability and potential drug resistance mechanisms. In this scenario, systems biology holds promise to accelerate validation and qualification for clinical trial contexts of use—including proof-of-mechanism, patient selection, assessment of treatment efficacy and safety rates, and prognostic evaluation. Albeit in their infancy, systems biology-based approaches are poised to identify relevant AD “signatures” through multifactorial and interindividual variability, allowing us to decipher disease pathophysiology and etiology.disease-modifying drugs.
KW - Alzheimer’s disease
KW - Biomarker-drug codevelopment
KW - Blood-based biomarker
KW - Clinical trial
KW - Context of use
KW - Pathophysiology
KW - Precision medicine
KW - Predictive biomarker
KW - Systems biology
UR - http://www.scopus.com/inward/record.url?scp=85073655577&partnerID=8YFLogxK
U2 - 10.31887/DCNS.2019.21.2/hhampel
DO - 10.31887/DCNS.2019.21.2/hhampel
M3 - Article
C2 - 31636492
AN - SCOPUS:85073655577
SN - 1294-8322
VL - 21
SP - 177
EP - 191
JO - Dialogues in Clinical Neuroscience
JF - Dialogues in Clinical Neuroscience
IS - 2
ER -