Project

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Precision-Medicine for Neurological Disorders: Harnessing the Power of Big Data and Machine Learning for Biomarker Discovery and Drug Repositioning Strategies

Applicant Jutzeler Catherine
Number 186101
Funding scheme Ambizione
Research institution Computational Systems Biology Department of Biosystems, D-BSSE ETH Zürich
Institution of higher education ETH Zurich - ETHZ
Main discipline Clinical Pathophysiology
Start/End 01.01.2020 - 31.12.2023
Approved amount 620'764.00
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All Disciplines (2)

Discipline
Clinical Pathophysiology
Infectious Diseases

Keywords (5)

Spinal Cord Injury; Polypharmacy; Neurological disorders; Machine Learning; Precision medicine

Lay Summary (German)

Lead
Bis heute ist die Suche nach einer Heilung für schwere traumatische Hirn- (auch Schädel-Hirn Trauma genannt) und Rückenmarkverletzungen sehr schwierig - unteranderem auch, weil diese Verletzungen sehr komplex sind. Dieses Projekt leistet einen Beitrag dazu, diese Verletzungen besser zu verstehen und neue Therapieansätze zu erforschen
Lay summary

Inhalt und Ziele des Forschungsprojekts

Unser übergeordnetes Ziel ist zu einem verbesserten Verständnis von traumatischen Hirn- und Rückenmarkverletzungen und deren Behandlung beizutragen. Im Detail werden wir grosse Datenmengen mit neusten Analyseverfahren auswerten, um (i) diese Verletzungen besser zu charakterisieren und (ii) Risikofaktoren, welche zu solchen Verletzungen führen, zu bestimmen. (iii) Des Weiteren wollen wir diejenigen Medikamente identifizieren, welche zur Behandlung von Komplikationen (wie zum Beispiel Schmerzen und Blasenprobleme) verabreicht werden, die Genesung verbessern oder verschlechtern. Medikamente, welche die Genesung verbessern, sind ideale Kandidaten für neue Therapieansätze. Jedoch ist es vor allem wichtig, die Medikamente zu kennen, welche die Genesung negativ beeinträchtigen (können), sodass auf diese in Zukunft verzichtet werden kann.

 

Wissenschaftlicher und gesellschaftlicher Kontext des Forschungsprojekts

Unsere Arbeit wird neue und wichtige Informationen liefern inwiefern Medikamente, welche für die Behandlung von gesundheitlichen Komplikationen verabreicht werden, die Genesung nach einer traumatischen Hirn- oder Rückenmarkverletzung beeinflussen. Diese Ergebnisse werden es Ärzten und Ärztinnen erlauben, die Behandlung solcher traumatischen Verletzungen und assoziierte Komplikationen zu verbessern, so dass die Genesung nicht beeinträchtigt wird.

Direct link to Lay Summary Last update: 29.08.2019

Responsible applicant and co-applicants

Employees

Publications

Publication
An intensity matched comparison of laser- and contact heat evoked potentials
De Schoenmacker Iara, Berry Carson, Blouin Jean-Sébastien, Rosner Jan, Hubli Michèle, Jutzeler Catherine R., Kramer John L. K. (2021), An intensity matched comparison of laser- and contact heat evoked potentials, in Scientific Reports, 11(1), 6861-6861.
Natural Progression of Routine Laboratory Markers after Spinal Trauma: A Longitudinal, Multi-Cohort Study
Bourguignon Lucie, Vo Anh Khoa, Tong Bobo, Geisler Fred, Mach Orpheus, Maier Doris, Kramer John L.K., Grassner Lukas, Jutzeler Catherine R. (2021), Natural Progression of Routine Laboratory Markers after Spinal Trauma: A Longitudinal, Multi-Cohort Study, in Journal of Neurotrauma, 38(15), 2151-2161.
Early Prediction of Sepsis in the ICU Using Machine Learning: A Systematic Review
Moor Michael, Rieck Bastian, Horn Max, Jutzeler Catherine R., Borgwardt Karsten (2021), Early Prediction of Sepsis in the ICU Using Machine Learning: A Systematic Review, in Frontiers in Medicine, 8(NA), NA.
Routine Blood Chemistry Predicts Functional Recovery After Traumatic Spinal Cord Injury: A Post Hoc Analysis
Leister Iris, Linde Lukas D., Vo Anh Khoa, Haider Thomas, Mattiassich Georg, Grassner Lukas, Schaden Wolfgang, Resch Herbert, Jutzeler Catherine R., Geisler Fred H., Kramer John L. K., Aigner Ludwig (2021), Routine Blood Chemistry Predicts Functional Recovery After Traumatic Spinal Cord Injury: A Post Hoc Analysis, in Neurorehabilitation and Neural Repair, 35(4), 321-333.
Serum albumin as a predictor of neurological recovery after spinal cord injury: a replication study
Vo Anh K., Geisler Fred, Grassner Lukas, Schwab Jan, Whiteneck Gale, Jutzeler Catherine, Kramer John L. K. (2021), Serum albumin as a predictor of neurological recovery after spinal cord injury: a replication study, in Spinal Cord, 59(3), 282-290.
The reporting of observational studies of drug effectiveness and safety: recommendations to extend existing guidelines
Cragg Jacquelyn J., Azoulay Laurent, Collins Gary, De Vera Mary A., Etminan Mahyar, Lalji Fawziah, Gershon Andrea S., Guyatt Gordon, Harrison Mark, Jutzeler Catherine, Kassam Rosemin, Kendzerska Tetyana, Lynd Larry, Mansournia Mohammad Ali, Sadatsafavi Mohsen, Tong Bobo, Warner Freda M., Tremlett Helen (2021), The reporting of observational studies of drug effectiveness and safety: recommendations to extend existing guidelines, in Expert Opinion on Drug Safety, 20(1), 1-8.
Single-trial averaging improves the physiological interpretation of contact heat evoked potentials
Jutzeler Catherine R., Linde Lukas D., Rosner Jan, Hubli Michèle, Curt Armin, Kramer John L.K. (2021), Single-trial averaging improves the physiological interpretation of contact heat evoked potentials, in NeuroImage, 225, 117473-117473.
Association of timing of gabapentinoid use with motor recovery after spinal cord injury
Warner Freda M., Cragg Jacquelyn J., Jutzeler Catherine R., Grassner Lukas, Mach Orpheus, Maier Doris D., Mach Benedikt, Schwab Jan M., Kopp Marcel A., Kramer John L.K. (2020), Association of timing of gabapentinoid use with motor recovery after spinal cord injury, in Neurology, 95(24), e3412-e3419.
Conditioned Pain Modulation Decreases Over Time in Patients With Neuropathic Pain Following a Spinal Cord Injury
Gagné Martin, Côté Isabelle, Boulet Mélanie, Jutzeler Catherine R., Kramer John L. K., Mercier Catherine (2020), Conditioned Pain Modulation Decreases Over Time in Patients With Neuropathic Pain Following a Spinal Cord Injury, in Neurorehabilitation and Neural Repair, 34(11), 997-1008.
The Effect of Conditioned Pain Modulation on Tonic Heat Pain Assessed Using Participant-Controlled Temperature
Sirucek Laura, Jutzeler Catherine Ruth, Rosner Jan, Schweinhardt Petra, Curt Armin, Kramer John Lawrence Kipling, Hubli Michèle (2020), The Effect of Conditioned Pain Modulation on Tonic Heat Pain Assessed Using Participant-Controlled Temperature, in Pain Medicine, 21(11), 2839-2849.
Machine learning for microbial identification and antimicrobial susceptibility testing on MALDI-TOF mass spectra: a systematic review
Weis C.V., Jutzeler C.R., Borgwardt K. (2020), Machine learning for microbial identification and antimicrobial susceptibility testing on MALDI-TOF mass spectra: a systematic review, in Clinical Microbiology and Infection, 26(10), 1310-1317.
Comorbidities, clinical signs and symptoms, laboratory findings, imaging features, treatment strategies, and outcomes in adult and pediatric patients with COVID-19: A systematic review and meta-analysis
Jutzeler Catherine R., Bourguignon Lucie, Weis Caroline V., Tong Bobo, Wong Cyrus, Rieck Bastian, Pargger Hans, Tschudin-Sutter Sarah, Egli Adrian, Borgwardt Karsten, Walter Matthias (2020), Comorbidities, clinical signs and symptoms, laboratory findings, imaging features, treatment strategies, and outcomes in adult and pediatric patients with COVID-19: A systematic review and meta-analysis, in Travel Medicine and Infectious Disease, 37, 101825-101825.
Excitatory and inhibitory responses in the brain to experimental pain: A systematic review of MR spectroscopy studies
Archibald Jessica, MacMillan Erin L., Enzler Alinda, Jutzeler Catherine R., Schweinhardt Petra, Kramer John L.K. (2020), Excitatory and inhibitory responses in the brain to experimental pain: A systematic review of MR spectroscopy studies, in NeuroImage, 215, 116794-116794.
Perfect Storm: COVID-19 Associated Cardiac Injury and Implications for Neurological Disorders
Jutzeler Catherine Ruth, Nightingale Thomas Edward, Krassioukov Andrei Vasilievich, Walter Matthias (2020), Perfect Storm: COVID-19 Associated Cardiac Injury and Implications for Neurological Disorders, in Neurotrauma Reports, 1(1), 2-4.

Collaboration

Group / person Country
Types of collaboration
Prof. Karsten Borgwardt Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
- Exchange of personnel
Prof. Dr. Adam Ferguson United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Prof. Dr. Armin Curt Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof. John Kramer Canada (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure

Awards

Title Year
2021 SCI Research Collaboration Grant 2021
Elected Member of the Swiss Young Academia (SYA) 2020
Translational Medicine and Biomedical Entrepreneurship 2020

Abstract

BACKGROUND AND RATIONALE: Traumatic neurological disorders, such as spinal cord injury (SCI) and traumatic brain injury (TBI), have a devastating impact on the patients, caregivers, and society, reducing quality of life and massively burdening the health care system. Countless clinical trials have failed to identify effective disorder-modifying treatments for patients suffering from SCI or TBI thus far. This is a growing problem because of the increased incidence of SCI and TBI in many countries, likely due to greater numbers of falls in elderly individual (i.e., ageing population) and concussion in sport- and military-related activities. However, prior to chasing new treatments, we need to reconsider the design of traditional clinical trials in traumatic neurological disorders. Furthermore, innovative drug discovery strategies, such as drug repositioning, have to be considered to expedite the development of effective treatments for patients with SCI and TBI.OVERALL OBJECTIVES AND METHODS: The first objective of the proposed research is, thus, to create and implement an innovative strategy to guide clinical trial designs as an alternative to the traditional “one-size-fits-all” approach. Specifically, this part of the project aims at analyzing high-dimensional datasets with machine-learning methods for biomarker identification in patients with SCI and TBI. Incorporating biomarkers into earlier phases of clinical trial development serves multiple purposes, ranging from informing patient stratification/ selection, safety and efficacy assessment, trial enrichment, to supporting the dose selection. The second objective is to identify commonly administered medications that modify neurological and functional recovery after acute SCI and TBI. The primary “innovative” method we are applying is observational drug effectiveness and safety studies. Observational studies will be performed using concomitant medication data from historical (i.e., Sygen and NASCIS) and contemporary data sources (i.e., TRACK-SCI, TRACK-TBI, CENTER-TBI). Drugs with beneficial effects should be considered as a potential therapy to enhance neurological or functional recovery. This would be possible through a drug repositioning strategy.EXPECTED RESULTS: The application of clustering methods (e.g., k-means clustering, topological data analysis) will identify common features amongst patients with SCI or TBI, respectively, and subsequently divide the initial heterogeneous population into disjoint and more homogeneous supergroups (i.e., clusters). We hypothesize that these subgroups exhibit different trajectories in terms of how the recover. For the second objective, we expect to find drugs that (alone or in combinations) will significantly impact (i.e., beneficial or detrimental) neurological recovery following SCI or TBI, while others won’t have any effect.IMPACT: The fundamental importance of the proposed project stems from the fact that even in the era of “modern” medicine traumatic neurological disorders (i.e., SCI and TBI) remain incurable, leaving millions of patients with permanent disabilities. Burdening the patient, caregivers, and the society as a whole, traumatic neurological disorders are one of the greatest threats to public health according to the World Health Organization (WHO). Thus, expediting the development of effective treatments constitutes a priority area of research for patients, but also the society as a whole. Biomarkers have the potential to enhance public health by novel means of understanding and diagnosing disorders, and providing strategies to determine responses to new treatments. Lastly, we are proposing an innovative and feasible approach that utilizes existing clinical trial data to identify drugs potentially modulating neurological recovery. Information gained from this study will be critical to best standards of care guidelines for the acute pharmacological management of SCI and TBI.
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