Documents in Process

The regeneration of myelin in the central nervous system (CNS) reinstates nerve health and function, yet its decreased efficiency with aging and progression of neurodegenerative disease contributes to axonal loss and/or degeneration. Although CNS myeloid cells have been implicated in regulating the efficiency of remyelination, the distinct contribution of blood monocytes versus that of resident microglia is unclear. [...]

In central nervous system (CNS) diseases characterized by late-onset neurodegeneration, the interplay between innate and adaptive immune responses remains poorly understood. This knowledge gap is exacerbated by the prolonged protracted disease course as it complicates the delineation of brain-resident and infiltrating cells. [...]

To develop a simplified smell test for identifying patients with Parkinson's disease (PD), we reevaluated the Sniffin'-Sticks-Identification-Test (SST-ID) and University-of-Pennsylvania-Smell-Identification-Test (UPSIT), using three case-control studies. These included 301 patients with PD or dementia with Lewy bodies (DLB), 68 subjects with multiple-system atrophy (MSA) or progressive supranuclear palsy (PSP), and 281 healthy controls (HC). [...]

Nanotechnology holds great promise for improving the delivery of therapeutics to the brain. However, current approaches often operate at the organ or tissue level and are limited by the lack of tools to dynamically monitor cargo delivery in vivo. [...]

In November 2018, the European Medicines Agency (EMA) restricted the use of fluoroquinolones (used by mouth, injections or inhalation) in the context of a referral due to long-lasting and potentially irreversible adverse drug reactions (ADRs). Fluoroquinolones should no longer be used to treat mild or moderate bacterial infections unless other antibacterials cannot be used.The first aim of our study was to analyze whether in the period before compared with after the referral the characteristics of spontaneous ADR reports related to fluoroquinolones differed and whether specific ADRs were more frequently reported for fluoroquinolones compared with cotrimoxazole. [...]

In this cumulative thesis, I present my research on transcriptomic-based drug repurposing in human viral infections describing an optimized workflow for drug prediction, in vitro validation and in vivo studies in clinical cohorts based on three publications.In the first publication, I took lead in a larger team effort to introduce a newly designed drug repurposing approach based on whole blood transcriptomics data and drug signatures databases, which was applied to identify potential drug candidates for treatment of patients across COVID-19 severity groups stratified based on clinical parameters and transcriptomic phenotypes (Aschenbrenner et al. 2021). [...]

Blood-brain barrier (BBB) disruptions are presumed to be implicated in schizophrenia-spectrum disorders (SSDs). Previous studies focused on cerebrospinal fluid (CSF) markers, which are imprecise for detecting subtle BBB disruption. [...]

Deep brain stimulation of the subthalamic nucleus (STN-DBS) effectively alleviates motor fluctuations in Parkinson's disease (PD). Optimal electrode placement and effective programming significantly influence outcomes. [...]

Alterations in glial cell function and cytokine levels in the central nervous system may be influenced by neuroinflammatory processes, which have a pathogenic role in psychiatric disorders. Variability in genes that encode inflammatory mediators is associated with risk of developing mental disorders. [...]