Phenotype-Agnostic Molecular Subtyping of Neurodegenerative Disorders: The Cincinnati Cohort Biomarker Program (CCBP)
Year: 2020
Type: article
Abstract: 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.
Source: Frontiers in Aging Neuroscience
Authors: Andrea Sturchio, Luca Marsili, Joaquin A. Vizcarra, Alok K. Dwivedi, Marcelo A. Kauffman, Andrew P. Duker, Peixin Lu, Michael W. Pauciulo, 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, Alberto J. Espay
Institutions: University of Cincinnati, Texas Tech University Health Sciences Center, Consejo Nacional de Investigaciones Científicas y Técnicas, Austral University, Universidad de Buenos Aires, Hospital Ramos Mejía, Cincinnati Children's Hospital Medical Center, Wuhan University, University of Cincinnati Medical Center, San Francisco VA Medical Center, University of California, San Francisco, Karolinska Institutet, Leiden University, MIT Media Lab, Massachusetts Institute of Technology, University of Birmingham
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,950
OpenAlex ID: W3091790184