B2B-RARE: Bench to Bedside – Rapid Diagnosis and Personalized Treatment of Rare Neuromuscular Diseases 28.10.202412’For the German version of the article, see here.NRW, 28th October 2024 – More than 400 genetically determined neuromuscular diseases (NME) are rare diseases.What unites them is the often early death or a considerable physical impairment of those affected. So far, only a handful of these NMEs have therapies at all. The consortium “B2B-RARE – Bench to Bedside” wants to change this and has received funding commitment in the field of innovative medicine, health and life sciences as part of the innovation competition Gesunder.IN.NRW.The project of the same name, which is funded with more than 2.6 million euros from European and state funds, aims to develop market-ready diagnostic and therapeutic procedures for rare neuromuscular diseases (NME) over the next three years using skin cells obtained from patients. Researchers at Heinrich Heine University Düsseldorf, University Medical Center Essen, BG University Hospital Bergmannsheil Bochum, Singleron Biotechnologies GmbH, Leibniz Institute for Analytical Sciences – ISAS e.V. and Lead Discovery Center GmbH will work together in an interdisciplinary manner.The project involves the development of personalized therapies for patients with rare NME, for whom treatment options are currently lacking.Patients also include children and young adults who previously had no prospect of a cure or at least relief from the disease. New therapeutic approaches are to be developed for them, which can be transferred directly into individual healing attempts in the sense of a “bench-to-bedside” principle (from the laboratory to the bedside). To achieve precision medicine 2.0 so-called omics technologies and bioinformatics including artificial intelligence (AI) are used to identify therapeutically relevant disease mechanisms and transfer them into clinical application.The starting point for this approach is patient selection, analysis of skin biopsies and subsequent phenotyping (classification of appearance) of the skin cells obtained (more precisely: fibroblasts). This phenotyping, which will be carried out by scientists in Düsseldorf, Bochum and Essen, will lead to an understanding of the underlying properties of these cells. Since skin cells carry the same genetic information as muscle cells, their disease-causing changes can be studied with omics technologies. Omics refers to the holistic characterization of all genes, proteins or metabolites (metabolic products), among other things. Omics data provide an important starting point in personalized medicine, as it provides information about individual disease processes and possible therapeutic approaches. The company Singleron will carry out the underlying gene activities (so-called transcriptome analyses), while ISAS researchers will analyze the corresponding proteins and metabolites on the basis of specially developed mass spectrometry methods.Search for already known and unknown active pharmaceutical ingredientsBioinformaticians at ISAS will then evaluate the omics data obtained with the help of AI and compare it with databases of existing active pharmaceutical ingredients. The aim of these analyses is to find suitable, already known active substances that can be used to address the dysregulated cellular processes identified in the first step in NME – and thus to be used for the treatment of patients; can be considered inside. In addition, the Lead Discovery Center will search for other potentially effective substances. Both the new and already known active ingredients are then tested in the laboratory on the fibroblasts obtained. In a further step, the scientists will test the relevance of the dysregulated cellular processes in nerve and muscle cells. Promising substances are then to be used directly in the clinics for personalized treatment in individual healing attempts in the patients.Overall, the consortium of clinicians, basic scientists and bioinformaticians focuses on both medical and social benefits in this research project. Improving the quality of life of NME patients through new personalized therapies not only has a positive impact on individual patients, but also on their families and the entire social environment.Overview of the project partnersUnder the leadership of Prof. Dr. Tobias Ruck from Heinrich Heine University Düsseldorf, the consortium brings together leading medical research institutions and industrial companies. This synergistic novel approach enables innovative therapeutic strategies for faster diagnosis and treatment of NME. Central to these goals is intensive cooperation between the project partners:Heinrich Heine University Düsseldorf, Department of Neurology (represented by Prof. Dr. Tobias Ruck, Dr. Christopher Nelke, Dr. Christina Menskes and Dr. Menekse Öztürk)University Medical Center Essen, Department of Neuropediatrics (represented by Prof. Dr. Ulrike Schara-Schmidt and PD Dr. Andreas Roos)BG University Hospital Bergmannsheil Bochum (represented by Prof. Dr. Matthias Vorgerd and Dr. Anne Güttsches)Singleron Biotechnologies GmbH, Cologne (represented by Dr. Nan Fang and Petro Leka)Leibniz Institute for Analytical Sciences – ISAS e.V. (represented by Prof. Dr. Albert Sickmann and Prof. Dr. Robert Heyer)Lead Discovery Center GmbH (LDC), Dortmund (represented by Anne-Katrin Klebl)About the Department of Neurology at the University Hospital DüsseldorfIn the Clinic for Neurology of the University Hospital Düsseldorf (Clinic Director: Prof. Dr. med. Dr. rer. nat. Sven Meuth; Deputy: Prof. Dr. med. Tobias Ruck), the entire spectrum of neurological diseases in adults aged 18 and over is diagnosed and treated. In total, the Department of Neurology treats about 15000 inpatients and outpatients every year (about 2000-2500 patients with neuromuscular diseases). The clinic is part of the Neuromuscular Center North Rhine. In addition, the Department of Neurology is a certified myasthenia center. In our clinic, we pursue the concept of close networking of patient care, clinical research and basic science. We hope to better understand the causes of neurological diseases and to develop new therapeutic options. The intensive involvement in international studies gives us the opportunity to provide patients with access to the latest innovative therapies.Further information at https://www.uniklinik-duesseldorf.de/patienten-besucher/klinikeninstitutezentren/klinik-fuer-neurologie.About the Neurological Clinic and Polyclinic of the BG University Hospital BergmannsheilThe Neurological Clinic and Polyclinic of the BG University Hospital Bergmannsheil (interim director Prof. Dr. med. Matthias Vorgerd) deals with a wide range of clinical and basic scientific research in addition to the clinical care of all neurological diseases of patients aged 18 and over. The clinic is part of the Ruhr Area Muscle Centre and a neuromuscular centre certified by the German Society for Muscle Diseases (DGM). She is involved in various national and international studies. In addition, the clinic has its own neuromuscular laboratory, where diagnostic and scientific examinations are carried out on the removed skeletal muscle, nerves and skin. A special focus is on research into neuromuscular diseases (NME), which is mainly based on the examination of muscle, nerve and skin biopsies. The research activities in the field of NME are funded by the Heimer Institute for Muscle Research, which is part of the organizational structure of the Neurological Clinic. This close networking of clinical work, specialized laboratory diagnostics and basic scientific research is intended to contribute to the development of new treatment options.About the Department of Neuropediatrics at the University Medical Center Essen AöRIn addition to the routine diagnostic analysis of the muscles of patients, the Department of Neuropediatrics also deals with research into the molecular causes of the respective clinical pictures. These include the identification of new genes and the analysis of the biochemical causes of neurodegenerative and muscular diseases. PD Dr. rer. Nat. Andreas Roos (Adjunct Professor at the University of Ottawa) and Prof. Dr. med. Ulrike Schara-Schmidt supervise the research activities of the neuromuscular laboratory. Research interests of the muscle laboratory are the identification of pathomechanisms and biomarkers for neuromuscular diseases with a pronounced focus on the use of patient material. The focus is also on the use of biomaterials, which can be obtained in a minimally invasive manner.In the context of translational processes, the neuromuscular laboratory is the subject of numerous national and international studies (https://clinicaltrials.gov/) as well as in overarching national and international studies on genotype-phenotype correlations.About the Leibniz Institute for Analytical Sciences – ISAS e.V. –The Leibniz Institute for Analytical Sciences – ISAS – e.V. develops high-performance analytical methods for health research. With its innovations, it contributes to improving the prevention, early diagnosis and treatment of diseases. The aim of the institute is to advance personalized therapy. To this end, ISAS combines knowledge from chemistry, biology, medicine, pharmacology, physics and computer science. The institute cooperates with national and international partners from science and industry. www.isas.deAbout Lead Discovery Center GmbHThe Lead Discovery Center GmbH was founded in 2008 by the technology transfer organization Max Planck Innovation to better exploit the potential of excellent basic research for the development of new, urgently needed drugs. LDC takes promising projects from academic research and typically develops them further to pharmaceutical lead structures (proof-of-concept in model systems) or to preclinical candidates. In close collaboration with leading partners from academia and industry, LDC is developing an extensive portfolio of projects in the field of small molecule drugs as well as therapeutic antibodies with exceptionally high medical and commercial potential.LDC maintains a close partnership with the Max Planck Society and the KHAN Technology Transfer Funds I + II (KHAN-I, -II). It has entered into numerous collaborations with various organizations worldwide, including AstraZeneca, Bayer, Boehringer Ingelheim, Merck KGaA, Qurient, invIOs, Cumulus Oncology, Nodus Oncology, JT Pharmaceuticals, KinSea AS and the Helmholtz Centers, for Infection Research (HZI) and the German Cancer Research Center (DKFZ). The LDC also works with leading academic drug discovery centers and investors to support start-ups.Further information: www.lead-discovery.deFor the latest updates about the project, visit the B2B-Rare website.Schnelle Diagnose und personalisierte Behandlung von seltenen neuromuskulären KrankheitenNRW, [28 Oktober, 2024] – Mehr als 400 genetisch bedingte neuromuskuläre Erkrankungen (NME) zählen zu den seltenen Erkrankungen. Was sie verbindet, ist das oftmals frühe Versterben oder eine erhebliche körperliche Beeinträchtigung der Betroffenen. Denn bislang gibt es nur für eine Handvoll dieser NME überhaupt Therapien. Das Konsortium „B2B-RARE – Bench to Bedside“ möchte dies ändern und hat im Rahmen des Innovationswettbewerbs Gesünder.IN.NRW eine Förderzusage im Bereich Innovative Medizin, Gesundheit und Lebenswissenschaften erhalten. Das mit mehr als 2,6 Mio. Euro aus europäischen und Landesmitteln geförderte gleichnamige Projekt will durch von Patient:innen gewonnene Hautzellen in den kommenden drei Jahren marktreife Diagnose- und Therapieverfahren für seltene neuromuskuläre Erkrankungen (NME) entwickeln.Dabei werden Forschende der Heinrich-Heine-Universität Düsseldorf, der Universitätsmedizin Essen, des BG Universitätsklinikum Bergmannsheil Bochum, des Leibniz-Institut für Analytische Wissenschaften – ISAS e.V., des Lead Discovery Center GmbH und von Singleron Biotechnologies GmbH interdisziplinär zusammenarbeiten. Das Projekt umfasst die Entwicklung personalisierter Therapien für Patienten mit seltenen NME, für die es derzeit keine Behandlungsmöglichkeiten gibt.Zu den Patienten gehören auch Kinder und junge Erwachsene, die bisher keine Aussicht auf Heilung oder zumindest Linderung der Krankheit hatten. Für sie sollen neue Therapieansätze entwickelt werden, die im Sinne eines „Bench-to-Bedside“-Prinzips (vom Labor zum Krankenbett) direkt in individuelle Heilungsversuche übertragen werden können. Um die Präzisionsmedizin 2.0 zu erreichen, werden sogenannte Omics-Technologien und Bioinformatik einschließlich künstlicher Intelligenz (KI) eingesetzt, um therapeutisch relevante Krankheitsmechanismen zu identifizieren und in die klinische Anwendung zu überführen.Ausgangspunkt für diesen Ansatz ist die Auswahl der Patienten, die Analyse von Hautbiopsien und die anschließende Phänotypisierung (Klassifizierung des Erscheinungsbildes) der gewonnenen Hautzellen (genauer: Fibroblasten). Diese Phänotypisierung, die von Wissenschaftlern in Düsseldorf, Bochum und Essen durchgeführt wird, soll zu einem Verständnis der zugrunde liegenden Eigenschaften dieser Zellen führen. Da Hautzellen die gleiche genetische Information tragen wie Muskelzellen, können ihre krankheitsverursachenden Veränderungen mit Omics-Technologien untersucht werden. Unter Omics versteht man die ganzheitliche Charakterisierung u.a. aller Gene, Proteine oder Metaboliten (Stoffwechselprodukte). Omics-Daten sind ein wichtiger Ansatzpunkt für die personalisierte Medizin, denn sie geben Aufschluss über individuelle Krankheitsprozesse und mögliche Therapieansätze. Die Firma Singleron wird die zugrundeliegenden Genaktivitäten (so genannte Transkriptomanalysen) durchführen, während die ISAS-Forscher die entsprechenden Proteine und Metaboliten auf der Basis speziell entwickelter massenspektrometrischer Methoden analysieren.Suche nach bereits bekannten und unbekannten pharmazeutischen WirkstoffenBioinformatiker des ISAS werten dann die mit Hilfe der KI gewonnenen Omics-Daten aus und vergleichen sie mit Datenbanken bestehender pharmazeutischer Wirkstoffe. Ziel dieser Analysen ist es, geeignete, bereits bekannte Wirkstoffe zu finden, mit denen die im ersten Schritt der NME identifizierten dysregulierten zellulären Prozesse adressiert werden können – und damit für die Behandlung von Patienten eingesetzt werden können. Darüber hinaus wird das Lead Discovery Center nach weiteren potenziell wirksamen Substanzen suchen. Sowohl die neuen als auch bereits bekannte Wirkstoffe werden dann im Labor an den gewonnenen Fibroblasten getestet. In einem weiteren Schritt prüfen die Wissenschaftler die Relevanz der gestörten zellulären Prozesse in Nerven- und Muskelzellen. Vielversprechende Substanzen sollen dann direkt in den Kliniken zur personalisierten Behandlung bei individuellen Heilungsversuchen der Patienten eingesetzt werden. Insgesamt setzt das Konsortium aus Klinikern, Grundlagenwissenschaftlern und Bioinformatikern bei diesem Forschungsprojekt sowohl auf medizinischen als auch auf gesellschaftlichen Nutzen. Die Verbesserung der Lebensqualität von NME-Patienten durch neue personalisierte Therapien hat nicht nur positive Auswirkungen auf die einzelnen Patienten, sondern auch auf die Gesellschaft.Überblick über die ProjektpartnerUnter der Leitung von Prof. Dr. Tobias Ruck von der Heinrich-Heine-Universität Düsseldorf bringt das Konsortium führende medizinische Forschungseinrichtungen und Industrieunternehmen zusammen.Dieser synergetische, neuartige Ansatz ermöglicht innovative therapeutische Strategien zur schnelleren Diagnose und Behandlung von NME. Im Mittelpunkt steht dabei die intensive Zusammenarbeit zwischen den Projektpartnern:Heinrich-Heine-Universität Düsseldorf, Klinik für Neurologie (vertreten durch Prof. Dr. Tobias Ruck, Dr. Christopher Nelke, Dr. Christina Menskes und Dr. Menekse Öztürk)Universitätsklinikum Essen, Klinik für Neuropädiatrie (vertreten durch Prof. Dr. Ulrike Schara-Schmidt und PD Dr. Andreas Roos)BG Universitätsklinikum Bergmannsheil Bochum (vertreten durch Prof. Dr. Matthias Vorgerd und Dr. Anne Güttsches)Leibniz-Institut für Analytische Wissenschaften – ISAS e.V. (vertreten durch Prof. Dr. Albert Sickmann und Prof. Dr. Robert Heyer)Lead Discovery Center GmbH (LDC), Dortmund (vertreten durch Anne-Katrin Klebl)Singleron Biotechnologies GmbH, Köln (vertreten durch Dr. Nan Fang und Petro Leka)Weitere Informationen finden Sie hier.Check out our latest news and events Learn more 24.09.11 Singleron Launches New All-in-One sCelLiVE® Tissue Dissociation Kit for Skin Cologne, 11th September 2024 – Singleron announced the launch of sCelLiVE® Tissue Dissociation Kit (Skin) (sCelLiVE Skin), a new all-in-one solution for human and mouse skin tissue…. Read more 24.04.11 Bioinformatics Bootcamp Singleron Biotechnologies regularly offers 8-week bioinformatics beginner courses to support single cell sequencing users. No bioinformatics background required. 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24.09.11 Singleron Launches New All-in-One sCelLiVE® Tissue Dissociation Kit for Skin Cologne, 11th September 2024 – Singleron announced the launch of sCelLiVE® Tissue Dissociation Kit (Skin) (sCelLiVE Skin), a new all-in-one solution for human and mouse skin tissue…. Read more
24.04.11 Bioinformatics Bootcamp Singleron Biotechnologies regularly offers 8-week bioinformatics beginner courses to support single cell sequencing users. No bioinformatics background required. Limited seats available.Contact us at info@singleron.bio to receive further… Read more
24.02.02 Singleron Expands Global Presence with New Office and Laboratories in Michigan, USA Singleron, a pioneer in single cell multi-omics solutions, announces the opening of its latest office and labs in Ann Arbor, Michigan, USA, marking a strategic… Read more