TY - JOUR A1 - Schmidt, Marco F. A1 - Korb, Oliver A1 - Abell, Chris T1 - Antagonists of the miRNA-Argonaute 2 Protein Complex BT - Anti-miR-AGOs JF - Drug Target miRNA: Methods and Protocols N2 - microRNAs (miRNAs) have been identified as high-value drug targets. A widely applied strategy in miRNA inhibition is the use of antisense agents. However, it has been shown that oligonucleotides are poorly cell permeable because of their complex chemical structure and due to their negatively charged backbone. Consequently, the general application of oligonucleotides in therapy is limited. Since miRNAs’ functions are executed exclusively by the Argonaute 2 protein, we therefore describe a protocol for the design of a novel miRNA inhibitor class: antagonists of the miRNA-Argonaute 2 protein complex, so-called anti-miR-AGOs, that not only block the crucial binding site of the target miRNA but also bind to the protein’s active site. Due to their lower molecular weight and, thus, more drug-like chemical structure, the novel inhibitor class may show better pharmacokinetic properties than reported oligonucleotide inhibitors, enabling them for potential therapeutic use. KW - Drug design KW - microRNA KW - miRNA-Argonaute 2 protein complex KW - miRNA inhibitors KW - miRNA seed region Y1 - 2016 SN - 978-1-4939-6563-2 SN - 978-1-4939-6561-8 SN - 978-1-4939-8236-3 U6 - https://doi.org/10.1007/978-1-4939-6563-2_17 SN - 1064-3745 SN - 1940-6029 VL - 1517 SP - 239 EP - 249 PB - Springer CY - New York ER - TY - JOUR A1 - Schmidt, Marco F. T1 - miRNA Targeting Drugs BT - the next blockbusters? JF - Drug Target miRNA: Methods and Protocols N2 - Only 20 years after the discovery of small non-coding, single-stranded ribonucleic acids, so-called microRNAs (miRNAs), as post-transcriptional gene regulators, the first miRNA-targeting drug Miravirsen for the treatment of hepatitis C has been successfully tested in clinical Phase II trials. Addressing miRNAs as drug targets may enable the cure, or at least the treatment of diseases, which presently seems impossible. However, due to miRNAs’ chemical structure, generation of potential drug molecules with necessary pharmacokinetic properties is still challenging and requires a re-thinking of the drug discovery process. Therefore, this chapter highlights the potential of miRNAs as drug targets, discusses the challenges, and tries to give a complete overview of recent strategies in miRNA drug discovery. KW - miRNA KW - Drug discovery KW - microRNA-induced silencing complex KW - Antisense agents KW - Small-molecule miRNA modulators KW - Argonaute 2 protein Y1 - 2016 SN - 978-1-4939-6563-2 SN - 978-1-4939-6561-8 U6 - https://doi.org/10.1007/978-1-4939-6563-2_1 SN - 1064-3745 SN - 1940-6029 VL - 1517 SP - 3 EP - 22 PB - Springer CY - New York ER - TY - CHAP A1 - Schmidt, Marco F. ED - Schmidt, Marco F. T1 - Preface T2 - Drug target miRNA Y1 - 2016 SN - 978-1-4939-6563-2 SN - 978-1-4939-6561-8 U6 - https://doi.org/10.1007/978-1-4939-6563-2 SN - 1064-3745 SN - 1940-6029 VL - 1517 SP - V EP - V PB - Springer CY - New York ER - TY - JOUR A1 - Schmidt, Marco A1 - Badtke, Gernot A1 - Bittmann, Frank N. T1 - Inhibitionen im neuromuskulären Reflexbogen als ein Faktor für rezidivierende Sportverletzungen und Überlastungsfolgen Y1 - 2003 ER - TY - JOUR A1 - Badtke, Gernot A1 - Bittmann, Frank N. A1 - Schmidt, Marco T1 - Inhibitionen in neuromuskulären Reflexbogen als Faktor für redivierende Sportverletzungen und Überlastungsfolgen Y1 - 2002 ER - TY - JOUR A1 - Cope, Justin L. A1 - Baukmann, Hannes A. A1 - Klinger, Jörn E. A1 - Ravarani, Charles N. J. A1 - Böttinger, Erwin A1 - Konigorski, Stefan A1 - Schmidt, Marco F. T1 - Interaction-based feature selection algorithm outperforms polygenic risk score in predicting Parkinson’s Disease status JF - Frontiers in genetics N2 - Polygenic risk scores (PRS) aggregating results from genome-wide association studies are the state of the art in the prediction of susceptibility to complex traits or diseases, yet their predictive performance is limited for various reasons, not least of which is their failure to incorporate the effects of gene-gene interactions. Novel machine learning algorithms that use large amounts of data promise to find gene-gene interactions in order to build models with better predictive performance than PRS. Here, we present a data preprocessing step by using data-mining of contextual information to reduce the number of features, enabling machine learning algorithms to identify gene-gene interactions. We applied our approach to the Parkinson's Progression Markers Initiative (PPMI) dataset, an observational clinical study of 471 genotyped subjects (368 cases and 152 controls). With an AUC of 0.85 (95% CI = [0.72; 0.96]), the interaction-based prediction model outperforms the PRS (AUC of 0.58 (95% CI = [0.42; 0.81])). Furthermore, feature importance analysis of the model provided insights into the mechanism of Parkinson's disease. For instance, the model revealed an interaction of previously described drug target candidate genes TMEM175 and GAPDHP25. These results demonstrate that interaction-based machine learning models can improve genetic prediction models and might provide an answer to the missing heritability problem. KW - epistasis KW - machine learning KW - feature selection KW - parkinson's disease KW - PPMI (parkinson's progression markers initiative) Y1 - 2021 U6 - https://doi.org/10.3389/fgene.2021.744557 SN - 1664-8021 VL - 12 PB - Frontiers Media CY - Lausanne ER - TY - JOUR A1 - Badtke, Gernot A1 - Bittmann, Frank N. A1 - Schmidt, Marco A1 - Steuer, M T1 - Ein neues Verfahren zur objektiven Bestimmung der äußeren Wirbelsäulenkurvatur in der Sagittalebene Y1 - 1997 ER - TY - JOUR A1 - Schmidt, Marco A1 - Bittmann, Frank N. A1 - Lazik, Dieter T1 - Untersuchungen des Zusammenhangs von äußerer Wirbelsäulenkurvatur und Funktion der posturalen Muskulatur Y1 - 1997 SN - 1026-079X ER - TY - BOOK A1 - Schmidt, Marco A1 - Badtke, Gernot A1 - Bittmann, Frank N. A1 - Steuer, M. T1 - A new approach for objektive determination of the external spine profile in the sagittal plane Y1 - 1998 ER - TY - JOUR A1 - Schmidt, Marco A1 - Hennke, Thomas A1 - Knochel, Mira A1 - Kurten, Achim A1 - Hierholzer, Johannes A1 - Daniel, Peter A1 - Bittmann, Frank N. T1 - Can chronic irritations of the trigeminal nerve cause musculoskeletal disorders? N2 - In this article, five cases of odontogenous dysfunctions and musculoskeletal complaints are presented. A common finding in all patients of this study was that the presence of joint complaints was related to deficits in the corresponding muscular function. These deficits were determined by manual muscle tests as described by Kendall et al. [Muscles - Testing and Function, ed 4. Baltimore, Williams and Wilkins, 1993] and were eliminated immediately by a neural therapeutic test injection into the disturbed dental region. The therapy provided solely aimed to eliminate the odontogenous dysfunction. No other therapeutic measures were carried out with regard to the patients' respective muscle, tendon, or joint complaints. Y1 - 2010 UR - http://content.karger.com/ProdukteDB/produkte.asp?Aktion=Ausgabe&Ausgabe=254389&ProduktNr=224242 U6 - https://doi.org/10.1159/000315338 SN - 1021-7096 ER - TY - THES A1 - Schmidt, Marco T1 - Objektive Bestimmung der äußeren Wirbelsäulenkontur in der Sagittalebene : funktionelle Interaktionen geometrischer und statischer Merkmale von Wirbelsäulenkonturen Y1 - 1999 ER -