Phenotype-Agnostic Molecular Subtyping of Neurodegenerative Disorders: The Cincinnati Cohort Biomarker Program (CCBP)
Ongoing biomarker development programs have been designed to identify serologic or imaging signatures of clinico-pathologic entities, assuming distinct biological boundaries between them. Identified putative biomarkers have exhibited large variability and inconsistency between cohorts, and remain in...
Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2020-10-01
|
Series: | Frontiers in Aging Neuroscience |
Subjects: | |
Online Access: | https://www.frontiersin.org/article/10.3389/fnagi.2020.553635/full |
id |
doaj-6d424a4d86364f5683f8e545b0af57fb |
---|---|
record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Andrea Sturchio Luca Marsili Joaquin A. Vizcarra Alok K. Dwivedi Marcelo A. Kauffman Marcelo A. Kauffman Andrew P. Duker Peixin Lu Peixin Lu Michael W. Pauciulo Benjamin D. Wissel Benjamin D. Wissel Emily J. Hill Benjamin Stecher Elizabeth G. Keeling Achala S. Vagal Lily Wang David B. Haslam Matthew J. Robson Caroline M. Tanner Daniel W. Hagey Samir El Andaloussi Kariem Ezzat Ronan M. T. Fleming Long J. Lu Max A. Little Max A. Little Alberto J. Espay |
spellingShingle |
Andrea Sturchio Luca Marsili Joaquin A. Vizcarra Alok K. Dwivedi Marcelo A. Kauffman Marcelo A. Kauffman Andrew P. Duker Peixin Lu Peixin Lu Michael W. Pauciulo Benjamin D. Wissel Benjamin D. Wissel Emily J. Hill Benjamin Stecher Elizabeth G. Keeling Achala S. Vagal Lily Wang David B. Haslam Matthew J. Robson Caroline M. Tanner Daniel W. Hagey Samir El Andaloussi Kariem Ezzat Ronan M. T. Fleming Long J. Lu Max A. Little Max A. Little Alberto J. Espay Phenotype-Agnostic Molecular Subtyping of Neurodegenerative Disorders: The Cincinnati Cohort Biomarker Program (CCBP) Frontiers in Aging Neuroscience biomarkers Parkinson’s disease Alzheimer’s disease neurodegeneration cohort drug repurposing |
author_facet |
Andrea Sturchio Luca Marsili Joaquin A. Vizcarra Alok K. Dwivedi Marcelo A. Kauffman Marcelo A. Kauffman Andrew P. Duker Peixin Lu Peixin Lu Michael W. Pauciulo Benjamin D. Wissel Benjamin D. Wissel Emily J. Hill Benjamin Stecher Elizabeth G. Keeling Achala S. Vagal Lily Wang David B. Haslam Matthew J. Robson Caroline M. Tanner Daniel W. Hagey Samir El Andaloussi Kariem Ezzat Ronan M. T. Fleming Long J. Lu Max A. Little Max A. Little Alberto J. Espay |
author_sort |
Andrea Sturchio |
title |
Phenotype-Agnostic Molecular Subtyping of Neurodegenerative Disorders: The Cincinnati Cohort Biomarker Program (CCBP) |
title_short |
Phenotype-Agnostic Molecular Subtyping of Neurodegenerative Disorders: The Cincinnati Cohort Biomarker Program (CCBP) |
title_full |
Phenotype-Agnostic Molecular Subtyping of Neurodegenerative Disorders: The Cincinnati Cohort Biomarker Program (CCBP) |
title_fullStr |
Phenotype-Agnostic Molecular Subtyping of Neurodegenerative Disorders: The Cincinnati Cohort Biomarker Program (CCBP) |
title_full_unstemmed |
Phenotype-Agnostic Molecular Subtyping of Neurodegenerative Disorders: The Cincinnati Cohort Biomarker Program (CCBP) |
title_sort |
phenotype-agnostic molecular subtyping of neurodegenerative disorders: the cincinnati cohort biomarker program (ccbp) |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Aging Neuroscience |
issn |
1663-4365 |
publishDate |
2020-10-01 |
description |
Ongoing biomarker development programs have been designed to identify serologic or imaging signatures of clinico-pathologic entities, assuming distinct biological boundaries between them. Identified putative biomarkers have exhibited large variability and inconsistency between cohorts, and remain inadequate for selecting suitable recipients for potential disease-modifying interventions. We launched the Cincinnati Cohort Biomarker Program (CCBP) as a population-based, phenotype-agnostic longitudinal study. While patients affected by a wide range of neurodegenerative disorders will be deeply phenotyped using clinical, imaging, and mobile health technologies, analyses will not be anchored on phenotypic clusters but on bioassays of to-be-repurposed medications as well as on genomics, transcriptomics, proteomics, metabolomics, epigenomics, microbiomics, and pharmacogenomics analyses blinded to phenotypic data. Unique features of this cohort study include (1) a reverse biology-to-phenotype direction of biomarker development in which clinical, imaging, and mobile health technologies are subordinate to biological signals of interest; (2) hypothesis free, causally- and data driven-based analyses; (3) inclusive recruitment of patients with neurodegenerative disorders beyond clinical criteria-meeting patients with Parkinson’s and Alzheimer’s diseases, and (4) a large number of longitudinally followed participants. The parallel development of serum bioassays will be aimed at linking biologically suitable subjects to already available drugs with repurposing potential in future proof-of-concept adaptive clinical trials. Although many challenges are anticipated, including the unclear pathogenic relevance of identifiable biological signals and the possibility that some signals of importance may not yet be measurable with current technologies, this cohort study abandons the anchoring role of clinico-pathologic criteria in favor of biomarker-driven disease subtyping to facilitate future biosubtype-specific disease-modifying therapeutic efforts. |
topic |
biomarkers Parkinson’s disease Alzheimer’s disease neurodegeneration cohort drug repurposing |
url |
https://www.frontiersin.org/article/10.3389/fnagi.2020.553635/full |
work_keys_str_mv |
AT andreasturchio phenotypeagnosticmolecularsubtypingofneurodegenerativedisordersthecincinnaticohortbiomarkerprogramccbp AT lucamarsili phenotypeagnosticmolecularsubtypingofneurodegenerativedisordersthecincinnaticohortbiomarkerprogramccbp AT joaquinavizcarra phenotypeagnosticmolecularsubtypingofneurodegenerativedisordersthecincinnaticohortbiomarkerprogramccbp AT alokkdwivedi phenotypeagnosticmolecularsubtypingofneurodegenerativedisordersthecincinnaticohortbiomarkerprogramccbp AT marceloakauffman phenotypeagnosticmolecularsubtypingofneurodegenerativedisordersthecincinnaticohortbiomarkerprogramccbp AT marceloakauffman phenotypeagnosticmolecularsubtypingofneurodegenerativedisordersthecincinnaticohortbiomarkerprogramccbp AT andrewpduker phenotypeagnosticmolecularsubtypingofneurodegenerativedisordersthecincinnaticohortbiomarkerprogramccbp AT peixinlu phenotypeagnosticmolecularsubtypingofneurodegenerativedisordersthecincinnaticohortbiomarkerprogramccbp AT peixinlu phenotypeagnosticmolecularsubtypingofneurodegenerativedisordersthecincinnaticohortbiomarkerprogramccbp AT michaelwpauciulo phenotypeagnosticmolecularsubtypingofneurodegenerativedisordersthecincinnaticohortbiomarkerprogramccbp AT benjamindwissel phenotypeagnosticmolecularsubtypingofneurodegenerativedisordersthecincinnaticohortbiomarkerprogramccbp AT benjamindwissel phenotypeagnosticmolecularsubtypingofneurodegenerativedisordersthecincinnaticohortbiomarkerprogramccbp AT emilyjhill phenotypeagnosticmolecularsubtypingofneurodegenerativedisordersthecincinnaticohortbiomarkerprogramccbp AT benjaminstecher phenotypeagnosticmolecularsubtypingofneurodegenerativedisordersthecincinnaticohortbiomarkerprogramccbp AT elizabethgkeeling phenotypeagnosticmolecularsubtypingofneurodegenerativedisordersthecincinnaticohortbiomarkerprogramccbp AT achalasvagal phenotypeagnosticmolecularsubtypingofneurodegenerativedisordersthecincinnaticohortbiomarkerprogramccbp AT lilywang phenotypeagnosticmolecularsubtypingofneurodegenerativedisordersthecincinnaticohortbiomarkerprogramccbp AT davidbhaslam phenotypeagnosticmolecularsubtypingofneurodegenerativedisordersthecincinnaticohortbiomarkerprogramccbp AT matthewjrobson phenotypeagnosticmolecularsubtypingofneurodegenerativedisordersthecincinnaticohortbiomarkerprogramccbp AT carolinemtanner phenotypeagnosticmolecularsubtypingofneurodegenerativedisordersthecincinnaticohortbiomarkerprogramccbp AT danielwhagey phenotypeagnosticmolecularsubtypingofneurodegenerativedisordersthecincinnaticohortbiomarkerprogramccbp AT samirelandaloussi phenotypeagnosticmolecularsubtypingofneurodegenerativedisordersthecincinnaticohortbiomarkerprogramccbp AT kariemezzat phenotypeagnosticmolecularsubtypingofneurodegenerativedisordersthecincinnaticohortbiomarkerprogramccbp AT ronanmtfleming phenotypeagnosticmolecularsubtypingofneurodegenerativedisordersthecincinnaticohortbiomarkerprogramccbp AT longjlu phenotypeagnosticmolecularsubtypingofneurodegenerativedisordersthecincinnaticohortbiomarkerprogramccbp AT maxalittle phenotypeagnosticmolecularsubtypingofneurodegenerativedisordersthecincinnaticohortbiomarkerprogramccbp AT maxalittle phenotypeagnosticmolecularsubtypingofneurodegenerativedisordersthecincinnaticohortbiomarkerprogramccbp AT albertojespay phenotypeagnosticmolecularsubtypingofneurodegenerativedisordersthecincinnaticohortbiomarkerprogramccbp |
_version_ |
1724751947207016448 |
spelling |
doaj-6d424a4d86364f5683f8e545b0af57fb2020-11-25T02:47:42ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652020-10-011210.3389/fnagi.2020.553635553635Phenotype-Agnostic Molecular Subtyping of Neurodegenerative Disorders: The Cincinnati Cohort Biomarker Program (CCBP)Andrea Sturchio0Luca Marsili1Joaquin A. Vizcarra2Alok K. Dwivedi3Marcelo A. Kauffman4Marcelo A. Kauffman5Andrew P. Duker6Peixin Lu7Peixin Lu8Michael W. Pauciulo9Benjamin D. Wissel10Benjamin D. Wissel11Emily J. Hill12Benjamin Stecher13Elizabeth G. Keeling14Achala S. Vagal15Lily Wang16David B. Haslam17Matthew J. Robson18Caroline M. Tanner19Daniel W. Hagey20Samir El Andaloussi21Kariem Ezzat22Ronan M. T. Fleming23Long J. Lu24Max A. Little25Max A. Little26Alberto J. Espay27James J. and Joan A. Gardner Family Center for Parkinson’s disease and Movement Disorders, Department of Neurology, University of Cincinnati, Cincinnati, OH, United StatesJames J. and Joan A. Gardner Family Center for Parkinson’s disease and Movement Disorders, Department of Neurology, University of Cincinnati, Cincinnati, OH, United StatesJames J. and Joan A. Gardner Family Center for Parkinson’s disease and Movement Disorders, Department of Neurology, University of Cincinnati, Cincinnati, OH, United StatesDivision of Biostatistics and Epidemiology, Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, United StatesConsultorio y Laboratorio de Neurogenética, Centro Universitario de Neurología “José María Ramos Mejía” y División Neurología, Hospital JM Ramos Mejía, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, ArgentinaPrograma de Medicina de Precision y Genomica Clinica, Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biomédicas, Universidad Austral– Consejo Nacional de Investigaciones Científicas y Técnicas de Argentina, Pilar, ArgentinaJames J. and Joan A. Gardner Family Center for Parkinson’s disease and Movement Disorders, Department of Neurology, University of Cincinnati, Cincinnati, OH, United StatesDivision of Biomedical Informatics, Cincinnati Children’s Hospital Medical Center, Department of Pediatrics, University of Cincinnati, Cincinnati, OH, United StatesSchool of Information Management, Wuhan University, Wuhan, ChinaDivision of Human Genetics, Cincinnati Children’s Hospital Medical Center, Department of Pediatrics, University of Cincinnati, Cincinnati, OH, United StatesJames J. and Joan A. Gardner Family Center for Parkinson’s disease and Movement Disorders, Department of Neurology, University of Cincinnati, Cincinnati, OH, United StatesDivision of Biomedical Informatics, Cincinnati Children’s Hospital Medical Center, Department of Pediatrics, University of Cincinnati, Cincinnati, OH, United StatesJames J. and Joan A. Gardner Family Center for Parkinson’s disease and Movement Disorders, Department of Neurology, University of Cincinnati, Cincinnati, OH, United StatesJames J. and Joan A. Gardner Family Center for Parkinson’s disease and Movement Disorders, Department of Neurology, University of Cincinnati, Cincinnati, OH, United StatesJames J. and Joan A. Gardner Family Center for Parkinson’s disease and Movement Disorders, Department of Neurology, University of Cincinnati, Cincinnati, OH, United StatesDepartment of Radiology, University of Cincinnati Medical Center, Cincinnati, OH, United StatesDepartment of Radiology, University of Cincinnati Medical Center, Cincinnati, OH, United StatesDivision of Infectious Diseases, Center for Inflammation and Tolerance, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United States0Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, Cincinnati, OH, United States1Department of Neurology, Weill Institute for Neurosciences, Parkinson’s Disease Research Education and Clinical Center, San Francisco Veteran’s Affairs Medical Center, University of California, San Francisco, San Francisco, CA, United States2Department of Laboratory Medicine, Clinical Research Center, Karolinska Institutet, Stockholm, Sweden2Department of Laboratory Medicine, Clinical Research Center, Karolinska Institutet, Stockholm, Sweden2Department of Laboratory Medicine, Clinical Research Center, Karolinska Institutet, Stockholm, Sweden3Analytical Biosciences, Division of Systems Biomedicine and Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, NetherlandsPrograma de Medicina de Precision y Genomica Clinica, Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biomédicas, Universidad Austral– Consejo Nacional de Investigaciones Científicas y Técnicas de Argentina, Pilar, Argentina4School of Computer Science, University of Birmingham, Birmingham, United Kingdom5Media Lab, Massachusetts Institute of Technology, Cambridge, MA, United StatesJames J. and Joan A. Gardner Family Center for Parkinson’s disease and Movement Disorders, Department of Neurology, University of Cincinnati, Cincinnati, OH, United StatesOngoing biomarker development programs have been designed to identify serologic or imaging signatures of clinico-pathologic entities, assuming distinct biological boundaries between them. Identified putative biomarkers have exhibited large variability and inconsistency between cohorts, and remain inadequate for selecting suitable recipients for potential disease-modifying interventions. We launched the Cincinnati Cohort Biomarker Program (CCBP) as a population-based, phenotype-agnostic longitudinal study. While patients affected by a wide range of neurodegenerative disorders will be deeply phenotyped using clinical, imaging, and mobile health technologies, analyses will not be anchored on phenotypic clusters but on bioassays of to-be-repurposed medications as well as on genomics, transcriptomics, proteomics, metabolomics, epigenomics, microbiomics, and pharmacogenomics analyses blinded to phenotypic data. Unique features of this cohort study include (1) a reverse biology-to-phenotype direction of biomarker development in which clinical, imaging, and mobile health technologies are subordinate to biological signals of interest; (2) hypothesis free, causally- and data driven-based analyses; (3) inclusive recruitment of patients with neurodegenerative disorders beyond clinical criteria-meeting patients with Parkinson’s and Alzheimer’s diseases, and (4) a large number of longitudinally followed participants. The parallel development of serum bioassays will be aimed at linking biologically suitable subjects to already available drugs with repurposing potential in future proof-of-concept adaptive clinical trials. Although many challenges are anticipated, including the unclear pathogenic relevance of identifiable biological signals and the possibility that some signals of importance may not yet be measurable with current technologies, this cohort study abandons the anchoring role of clinico-pathologic criteria in favor of biomarker-driven disease subtyping to facilitate future biosubtype-specific disease-modifying therapeutic efforts.https://www.frontiersin.org/article/10.3389/fnagi.2020.553635/fullbiomarkersParkinson’s diseaseAlzheimer’s diseaseneurodegenerationcohortdrug repurposing |