Faculty of Science Department of Pharmaceutical Sciences OverviewResearch UnitsPublicationsProjects & CollaborationsProjects & Collaborations OverviewResearch UnitsPublicationsProjects & CollaborationsProjects & Collaborations All types All types Projects [All projects]Umbrella ProjectResearch Project Institutional Research Networks [Institutional Research Networks]Research Networks of the University of BaselResearch Networks (Institutional Membership) Show only active 11 foundShow per page10 10 20 50 Design of antimicrobial peptides through active learning Research Project | 2 Project MembersNo Description available Psilocybin-induced synaptic plasticity: circuit mechanisms underlying the antidepressant potential of hallucinogens Research Project | 1 Project MembersPsilocybin induces hallucinations through its active metabolite psilocin, which acts as serotonin (5-HT) 2A receptor agonist. Although classified as drugs of abuse, psilocybin and other hallucinogens may be clinically used for several psychiatric disorders, including major depressive disorder. Preliminary clinical studies advocate administering single doses of psilocybin intermittently, based on the observation that a single dose induces long-lasting therapeutic effects. Neuronal plasticity may underlie these long-lasting effects. In humans, psilocybin acutely increases the activity of the prefrontal cortex, likely by facilitating thalamocortical signaling. This coincides with the localization of 5-HT 2A receptors, which are expressed in frontal cortex pyramidal cells postsynaptically and putatively in thalamic afferents on the presynaptic site. In rodent brain slices, 5-HT and various hallucinogens acutely increase synaptic strength of glutamate afferents onto cortical pyramidal neurons. Specific neuronal circuits and synapses that may be persistently changed after psilocybin have not been identified and we lack proof of causality for antidepressant efficacy. We will therefore examine synaptic plasticity in defined neuronal circuits as a mechanism underlying psilocybin's effect on anhedonia, a key symptom of depression. Further, we will investigate a simple, translational strategy to refine psilocybin pharmacotherapy. Akin to classical conditioning, pairing psilocybin treatment with a cue may allow recalling the therapeutic benefits through cue exposure when the initial drug effect wears off. This strategy could enhance the efficacy of psilocybin treatment sessions. This project builds on the hypotheses that psilocybin induces long-lasting forms of plasticity at thalamocortical synapses, which underlie its antidepressant-like effects, and that the potential therapeutic effect can be recalled through exposure to a drug-associated cue. We aim to identify neuronal circuits involved in psilocybin-induced long-term synaptic plasticity, establish psilocybin efficacy for antidepressant-like effects and elucidate the underlying mechanism, and provide evidence for recall of psilocybin effects through drug-cue conditioning that may be clinically translated. Optogenetics and whole-cell patch-clamp slice recordings will be used for celltype- and circuit-specific observations and manipulations. Behavioral testing of anhedonia in an anxiogenic environment will be applied, as this can report the antidepressant potential of a drug. This research will reveal the clinically relevant mode of action of psilocybin and provide blueprints for improved treatment strategies such as the supportive application of conditioned drug cues. ToxOligo2 - Toxicological properties of oligomers present in food contact materials Research Project | 6 Project MembersToxOligo addresses an important knowledge gap by evaluating toxicological properties of oligomers released from polymers as food contact materials (FCM). The formation and presence of oligomers is inevitable in such FCM. Despite known migration into food, these substances are toxicologically poorly characterized, preventing adequate risk assessment. The ongoing project phase allowed essential new insights into available information on oligomers from all polymeric FCM. A pilot study on PET helped to design an optimized strategy and workflow to address this task. Information on physicochemical, ADME and toxicological properties was collected using computational methods. In a second project phase, a collection of oligomers from all other materials will be made based on the obtained information. The focus will be on bioactivity assessment of these substances. Hazard profiles will be established using various in vitro assays to assess general toxicity, cellular stress pathways, macrophage activation and endocrine effects. These studies aim at assessing the level of concern of such substances and providing recommendations for prioritization of future toxicological testing. P3S: Physicians and pharmacists together improving patient's medication safety Research Project | 4 Project MembersArzneimittel sind wichtig für die erfolgreiche Behandlung von vielen Krankheiten. Sie können aber auch zu Problemen führen, besonders wenn mehrere Arzneimittel gleichzeitig und über längere Zeit verwendet werden. Arzneimittelbezogene Probleme (DRP) wie Medikationsfehler, unerwünschte Arzneimittelwirkungen (UAW) und Interaktionsprobleme sind häufig und habe oftmals unnötige, medizinisch gefährliche und teure Folgen. Interventionen zur Behebung von DRP wie ein systematischer Medikationsabgleich und Medikationsanalysen erfolgen, wenn überhaupt, häufig erst reaktiv bei einer Spitaleinweisung, obwohl 80-90% der Gesundheitsbetreuung im ambulanten Setting stattfinden. Deshalb ist es wichtig, regelmässig das Risiko für arzneimittelbezogene Probleme zu überprüfen. Dies geschieht am besten dort, wo Menschen mit Medikamenten am meisten Kontakt zu medizinischen Fachpersonen haben: Bei den Hausärztinnen und Hausärzten und in den Apotheken. Ein integrierter, strukturierter und interprofessioneller Prozess zur Therapieoptimierung bei Patienten mit hohem Risiko für DRP schafft Transparenz und in Anbetracht des Fachkräftemangels eine gleichbleibend hohe Behandlungsqualität für Patienten, Sicherheit für die Behandler und Kostenersparnisse. Bisher existieren in der Schweiz jedoch keine systematischen Ansätze für die interprofessionelle Zusammenarbeit zwischen Ärzten und Apothekern zur Optimierung der Arzneimittelsicherheit. Das Projekt «Physicians and pharmacists together improving patient's medication safety» (P 3 S) will die Zusammenarbeit zwischen diesen Fachpersonen verbessern, um arzneimittelbezogene Probleme zu verhindern. Dafür werden Risiken für arzneimittelbezogene Probleme durch eine regelmässige Abklärung in der Hausarztpraxis frühzeitig identifiziert. Bei einem erhöhten Risiko können aufgrund einer Medikationsanalyse in der Apotheke anschliessend gezielte Massnahmen zur Therapieoptimierung ergriffen werden. Die identifizierten Risiken, potenzielle und manifeste DRP sowie Optimierungsvorschläge und umgesetzte Massnahmen werden strukturiert erfasst und stehen als Basis für die kontinuierliche Verbesserung der Arzneimittelsicherheit zur Verfügung. Um eine nachhaltige Verbesserung zu erreichen, werden die Abläufe und Hilfsmittel im Rahmen des Projekts in enger Zusammenarbeit mit den Patienten und beteiligten Fachpersonen entwickelt und getestet. Anschliessend wird untersucht, wie die Abläufe erfolgreich in die Praxis an unterschiedlichen Standorten integriert werden können. Schlussendlich werden in einer Studie die Wirkung und Umsetzung wissenschaftlich geprüft. Das Projekt wird von der Eidgenössischen Qualitätskommission finanziell unterstützt und dauert von 1.1.2023 bis 31.12.2026. Biosynthesis, Enzymology and Biotechnology of Bacterial Aromatic Polyketide and Tropone Natural Products Research Project | 1 Project MembersLead Bakterielle aromatische Polyketide und Tropone sind Naturstoffe mit vielseitigen Bioaktivitäten, welche sowohl essentielle Rollen in der Natur einnehmen (beispielsweise im Rahmen symbiotischer Interaktionen), als auch potentielle Leitstrukturen für die Entwicklung von Wirkstoffkandidaten für medizinische Anwendungen sind. Die Biosynthese dieser Verbindungen ist oftmals nur unzulänglich beschrieben, insbesondere bezüglich der Bildung der teils komplexen Pharmakophore, sowie des Einbaus von sauerstoff- oder schwefelhaltigen funktionellen Gruppen. Ein besseres Verständnis über diese Prozesse könnte beispielsweise für die Herstellung neuartiger bioaktiver Abkömmlinge dieser Verbindungen ausgenutzt werden. Inhalt und Ziel des Forschungsprojekts Unsere primären Ziele sind es, die einzelnen enzymatischen Schritte der bakteriellen Biosynthese aromatischer Polyketide (wie der Rubromycine) sowie der Tropone (Tropodithietsäure und andere schwefelhaltige Tropone) im Detail zu verstehen, welche oftmals antibiotische oder krebshemmende Aktivitäten aufweisen. Im Falle der Polyketide beinhaltet dies die Untersuchung insbesondere sauerstoffübertragender Enzyme und deren ungewöhnlicher Regulation mittels Acetyltransferasen. Bei den Troponen soll hingegen der kryptische S-Einbau aufgeklärt werden, bevor Schlüsselenzyme aus den jeweiligen Biosynthesewegen bezüglich ihrer räumlichen Struktur und ihres Reaktionsmechanismus im Detail charakterisiert werden. Dieses Wissen wird daraufhin für die Herstellung neuartiger Derivate dieser Naturstoffklassen eingesetzt, welche zudem bezüglich ihrer Bioaktivitäten untersucht werden sollen. Wissenschaftlicher und gesellschaftlicher Kontext des Forschungsprojekts Unsere Arbeit wird neue Erkenntnisse über enzymatische Reaktionen liefern, die von zentraler Bedeutung für die Herstellung komplexer mikrobieller Naturstoffe sind. Das erworbene Wissen soll als Grundlage dienen, diese Enzyme gezielt einzusetzen und abzuändern, um neuartige bioaktive Verbindungen und somit potentielle Wirkstoffkandidaten herzustellen. Simulation in pharmacy education Research Project | 2 Project MembersIt is a challenge for pharmacy universities worldwide to combine theoretical knowledge with practical skills to equip students for their future practice. Simulation - either virtual or on-site - has expanded rapidly as new technique of learning. In July 2022 and for the first time in Switzerland, a fully equipped pharmacy has been installed at the Pharmazentrum, University of Basel, for simulation purposes. Scientific research is needed to establish simulation in the curriculum. This project aims at developing scenarios from clinical / pharmaceutical cases to be used by pharmacy students in simulation. Variables for the assessment of learning progress will be determined. A comparison with digital simulation is planned. SwissPandemic&AmR-Health Ecoomy Awareness Detect (SPEARHEAD) - SP1 Research Project | 3 Project MembersFighting Antimicrobial resistance through rapid digital pandemic response Our consortium of 8 public and 4 private Swiss institutions has joined forces to address the silent pandemic of antimicrobial resistance (AMR) by launching the 'Swiss Pandemic & AMR - Health Economy Awareness Detect' (SPEARHEAD) partnership. AMR is the ability of microorganisms (like bacteria, viruses, and some parasites) to prevent antimicrobials (such as antibiotics, antivirals and antimalarials) from working against them. As a result, many treatments are becoming ineffective against infections that were previously easily treatable. SPEARHEAD will leverage lessons learnt to address the steadily worsening, silent pandemic of AMR, with potentially 10M deaths per year globally by 2050 (4 x the 2020 COVID-19 death toll) and the related economic impact on society. Specificity, selectivity and pharmacokinetics of compstatin: a comprehensive multidisciplinary analysis Research Project | 6 Project MembersThe complement system plays a major role in innate immunity as it confers immune surveillance and first-line defense against non- or altered-self entities such as microbes or apoptotic cells. Yet, misguided complement activation may trigger or contribute to severe clinical conditions or complications, including autoimmune, hemolytic, inflammatory and age-related disorders and transplant rejection (PMID) [1]. Owing to its cascade organization, involving ~50 plasma proteins, receptors and enzymes, complement provides multiple points for novel pharmacological intervention [2]. However, few complement-targeted drugs have reached the clinic, and the available options primarily target peripheral steps in cascade initiation or effector generation. For many acute-phase or multifactorial complement disorders, blocking the activation of the central complement component C3 is considered important [3]. Derivatives of compstatin, a peptidic inhibitor of C3 activation [4], are the most advanced compounds in this class, with two candidate drugs being evaluated in clinical trials. However, its narrow species-specificity for primate C3 currently restricts a broader exploration of potential benefits of C3 inhibition in various established animal models of complement disorders. Furthermore, despite considerable progress in structure optimization, some pharmacokinetic and physicochemical properties of the compstatin class remain to be improved to fully unleash its unique therapeutic potential. The main objective of this project is to understand target binding and complement inhibition by compstatin in the human system at the atomic level and identify key determinants of its narrow species specificity. We will utilize this knowledge for designing compstatin analogs that recognize non-primate C3 and, for example, inhibit mouse, rat or pig complement. Simultaneously, we will assess compstatin's target selectivity for C3 over the orthologous C4 and C5 proteins and explore options for achieving C4-, C5- or pan-specific inhibitors for research or clinical applications. Finally, we will analyze and optimize the pharmacokinetic properties of compstatin with special emphasis on solubility and bioavailability. The proposed rationalization and optimization efforts will be driven by well-established in silico simulation techniques such as molecular dynamics simulations, free energy methods, homology modeling, and post-MD analyses, supported by novel approaches based on deep learning (Prof. Markus Lill, Computational Pharmacy). Thanks to project collaborations with strong experimental groups, in silico findings will be experimentally verified by employing peptide synthesis and characterization, chemical modification and labeling, and target binding and functional assays in vitro (Prof. Daniel Ricklin, Molecular Pharmacy) as well as pre-clinical assessments of cellular permeability in vitro and in vivo (Prof. Henriette Meyer zu Schwabedissen, Biopharmacy; all at University of Basel). Our studies are expected to extend preclinical evaluation options of compstatin-based drugs in animal models and enhance their pharmacokinetic profile, thereby facilitating clinical development of this important inhibitor class. Selectivity studies with C4/C5 may provide insight into complement activation and potentially reveal novel inhibitors. Finally, atomic level insight into the structure-activity/property relationships of cyclic peptides may be used for the design of this compound type in general. [1] Ricklin, D.; Reis, E. S.; Lambris, J. D. Complement in Disease: A Defence System Turning Offensive. Nat. Rev. Nephrol. 2016, 12 (7), 383-401. https://doi.org/10.1038/nrneph.2016.70. [2] Mastellos, D.C., Ricklin, D. & Lambris, J.D. Clinical promise of next-generation complement therapeutics. Nat Rev Drug Discov 18, 707-729 (2019). https://doi.org/10.1038/s41573-019-0031-6 [3] Mastellos, D. C.; Reis, E. S.; Ricklin, D.; Smith, R. J.; Lambris, J. D. Complement C3-Targeted Therapy: Replacing Long-Held Assertions with Evidence-Based Discovery. Trends Immunol. 2017, 38 (6), 383-394. https://doi.org/10.1016/j.it.2017.03.003. [4] Mastellos, D. C.; Yancopoulou, D.; Kokkinos, P.; Huber-Lang, M.; Hajishengallis, G.; Biglarnia, A. R.; Lupu, F.; Nilsson, B.; Risitano, A. M.; Ricklin, D.; Lambris, J. D. Compstatin: A C3-Targeted Complement Inhibitor Reaching Its Prime for Bedside Intervention. Eur. J. Clin. Invest. 2015, 45 (4), 423-440. https://doi.org/10.1111/eci.12419. m-Health ⁄ smartphone apps to foster adherence to medication Research Project | 2 Project MembersMedication adherence is a prerequisite to treatment outcomes. We will develop an Smartphone application aimed at fostering adherence to medication via mobile phone technology. Patients will record intakes and self-evaluate symptoms. Pharmacists will have a central role to play in interpreting the adherence data and delivering a targeted counseling. A report will be created that includes a pharmaceutical recommendation by the pharmacists and that will be shared with the physician. Physicians will be able to adjust treatment guided by adherence reports and self-evaluation of symptoms. Interprofessionality will be fostered. Feasibility study will be preformed with short-term PPI. A study on the epidemiology of treated glaucoma in the UK Research Project | 5 Project MembersBackground: Glaucoma is a group of progressive optic neuropathies that have in common a slow progressive neurodegeneration of retinal cells and their axons and a concomitant pattern of visual loss. The biological basis of the disease is not yet fully understood, and the factors contributing to its progression are not yet fully characterised. However, intraocular pressure is the only proven treatable risk factor. Glaucoma is the second most common cause of vision loss worldwide behind cataracts, but, unlike cataracts, the vision loss associated with glaucoma is largely irreversible. Among the major types of glaucoma are open-angle (OAG), angle-closure (ACG), secondary glaucoma, and glaucoma with onset in infancy. In 2010 it was estimated that 60.5 million people suffer with OAG or ACG worldwide. These numbers are expected to reach 79.6 million by 2020, and of these, 74% will have OAG. To our knowledge, incidence rates of glaucoma have not been quantified in the UK. Objective: We therefore aim to quantify, through an observational study, the treatment rates for glaucoma and intraocular hypertension (IOH) in the U.K. and compare demographic characteristics, comorbidities (e.g. obesity, diabetes, others), and lifestyle factors (smoking, alcohol consumption) between treated patients with and untreated (i.e., glaucoma-free) controls. Furthermore, we plan to conduct one ore more drug safety studies, using a case-control design, on the risk of glaucoma after exposure to certain drugs of interest. Additionally, we plan to assess the association between other chronic conditions and the risk of glaucoma. Methods: we will assess standardized treatement rates and perform stratified analyses for age, sex and region of the UK. We will further describe and compare pateint charcteristics with the general population. For the study of potential associations with glaucom we will use a case-control design and perform conditional logistic regression analyes. 12 12 OverviewResearch UnitsPublicationsProjects & Collaborations
Projects & Collaborations All types All types Projects [All projects]Umbrella ProjectResearch Project Institutional Research Networks [Institutional Research Networks]Research Networks of the University of BaselResearch Networks (Institutional Membership) Show only active 11 foundShow per page10 10 20 50 Design of antimicrobial peptides through active learning Research Project | 2 Project MembersNo Description available Psilocybin-induced synaptic plasticity: circuit mechanisms underlying the antidepressant potential of hallucinogens Research Project | 1 Project MembersPsilocybin induces hallucinations through its active metabolite psilocin, which acts as serotonin (5-HT) 2A receptor agonist. Although classified as drugs of abuse, psilocybin and other hallucinogens may be clinically used for several psychiatric disorders, including major depressive disorder. Preliminary clinical studies advocate administering single doses of psilocybin intermittently, based on the observation that a single dose induces long-lasting therapeutic effects. Neuronal plasticity may underlie these long-lasting effects. In humans, psilocybin acutely increases the activity of the prefrontal cortex, likely by facilitating thalamocortical signaling. This coincides with the localization of 5-HT 2A receptors, which are expressed in frontal cortex pyramidal cells postsynaptically and putatively in thalamic afferents on the presynaptic site. In rodent brain slices, 5-HT and various hallucinogens acutely increase synaptic strength of glutamate afferents onto cortical pyramidal neurons. Specific neuronal circuits and synapses that may be persistently changed after psilocybin have not been identified and we lack proof of causality for antidepressant efficacy. We will therefore examine synaptic plasticity in defined neuronal circuits as a mechanism underlying psilocybin's effect on anhedonia, a key symptom of depression. Further, we will investigate a simple, translational strategy to refine psilocybin pharmacotherapy. Akin to classical conditioning, pairing psilocybin treatment with a cue may allow recalling the therapeutic benefits through cue exposure when the initial drug effect wears off. This strategy could enhance the efficacy of psilocybin treatment sessions. This project builds on the hypotheses that psilocybin induces long-lasting forms of plasticity at thalamocortical synapses, which underlie its antidepressant-like effects, and that the potential therapeutic effect can be recalled through exposure to a drug-associated cue. We aim to identify neuronal circuits involved in psilocybin-induced long-term synaptic plasticity, establish psilocybin efficacy for antidepressant-like effects and elucidate the underlying mechanism, and provide evidence for recall of psilocybin effects through drug-cue conditioning that may be clinically translated. Optogenetics and whole-cell patch-clamp slice recordings will be used for celltype- and circuit-specific observations and manipulations. Behavioral testing of anhedonia in an anxiogenic environment will be applied, as this can report the antidepressant potential of a drug. This research will reveal the clinically relevant mode of action of psilocybin and provide blueprints for improved treatment strategies such as the supportive application of conditioned drug cues. ToxOligo2 - Toxicological properties of oligomers present in food contact materials Research Project | 6 Project MembersToxOligo addresses an important knowledge gap by evaluating toxicological properties of oligomers released from polymers as food contact materials (FCM). The formation and presence of oligomers is inevitable in such FCM. Despite known migration into food, these substances are toxicologically poorly characterized, preventing adequate risk assessment. The ongoing project phase allowed essential new insights into available information on oligomers from all polymeric FCM. A pilot study on PET helped to design an optimized strategy and workflow to address this task. Information on physicochemical, ADME and toxicological properties was collected using computational methods. In a second project phase, a collection of oligomers from all other materials will be made based on the obtained information. The focus will be on bioactivity assessment of these substances. Hazard profiles will be established using various in vitro assays to assess general toxicity, cellular stress pathways, macrophage activation and endocrine effects. These studies aim at assessing the level of concern of such substances and providing recommendations for prioritization of future toxicological testing. P3S: Physicians and pharmacists together improving patient's medication safety Research Project | 4 Project MembersArzneimittel sind wichtig für die erfolgreiche Behandlung von vielen Krankheiten. Sie können aber auch zu Problemen führen, besonders wenn mehrere Arzneimittel gleichzeitig und über längere Zeit verwendet werden. Arzneimittelbezogene Probleme (DRP) wie Medikationsfehler, unerwünschte Arzneimittelwirkungen (UAW) und Interaktionsprobleme sind häufig und habe oftmals unnötige, medizinisch gefährliche und teure Folgen. Interventionen zur Behebung von DRP wie ein systematischer Medikationsabgleich und Medikationsanalysen erfolgen, wenn überhaupt, häufig erst reaktiv bei einer Spitaleinweisung, obwohl 80-90% der Gesundheitsbetreuung im ambulanten Setting stattfinden. Deshalb ist es wichtig, regelmässig das Risiko für arzneimittelbezogene Probleme zu überprüfen. Dies geschieht am besten dort, wo Menschen mit Medikamenten am meisten Kontakt zu medizinischen Fachpersonen haben: Bei den Hausärztinnen und Hausärzten und in den Apotheken. Ein integrierter, strukturierter und interprofessioneller Prozess zur Therapieoptimierung bei Patienten mit hohem Risiko für DRP schafft Transparenz und in Anbetracht des Fachkräftemangels eine gleichbleibend hohe Behandlungsqualität für Patienten, Sicherheit für die Behandler und Kostenersparnisse. Bisher existieren in der Schweiz jedoch keine systematischen Ansätze für die interprofessionelle Zusammenarbeit zwischen Ärzten und Apothekern zur Optimierung der Arzneimittelsicherheit. Das Projekt «Physicians and pharmacists together improving patient's medication safety» (P 3 S) will die Zusammenarbeit zwischen diesen Fachpersonen verbessern, um arzneimittelbezogene Probleme zu verhindern. Dafür werden Risiken für arzneimittelbezogene Probleme durch eine regelmässige Abklärung in der Hausarztpraxis frühzeitig identifiziert. Bei einem erhöhten Risiko können aufgrund einer Medikationsanalyse in der Apotheke anschliessend gezielte Massnahmen zur Therapieoptimierung ergriffen werden. Die identifizierten Risiken, potenzielle und manifeste DRP sowie Optimierungsvorschläge und umgesetzte Massnahmen werden strukturiert erfasst und stehen als Basis für die kontinuierliche Verbesserung der Arzneimittelsicherheit zur Verfügung. Um eine nachhaltige Verbesserung zu erreichen, werden die Abläufe und Hilfsmittel im Rahmen des Projekts in enger Zusammenarbeit mit den Patienten und beteiligten Fachpersonen entwickelt und getestet. Anschliessend wird untersucht, wie die Abläufe erfolgreich in die Praxis an unterschiedlichen Standorten integriert werden können. Schlussendlich werden in einer Studie die Wirkung und Umsetzung wissenschaftlich geprüft. Das Projekt wird von der Eidgenössischen Qualitätskommission finanziell unterstützt und dauert von 1.1.2023 bis 31.12.2026. Biosynthesis, Enzymology and Biotechnology of Bacterial Aromatic Polyketide and Tropone Natural Products Research Project | 1 Project MembersLead Bakterielle aromatische Polyketide und Tropone sind Naturstoffe mit vielseitigen Bioaktivitäten, welche sowohl essentielle Rollen in der Natur einnehmen (beispielsweise im Rahmen symbiotischer Interaktionen), als auch potentielle Leitstrukturen für die Entwicklung von Wirkstoffkandidaten für medizinische Anwendungen sind. Die Biosynthese dieser Verbindungen ist oftmals nur unzulänglich beschrieben, insbesondere bezüglich der Bildung der teils komplexen Pharmakophore, sowie des Einbaus von sauerstoff- oder schwefelhaltigen funktionellen Gruppen. Ein besseres Verständnis über diese Prozesse könnte beispielsweise für die Herstellung neuartiger bioaktiver Abkömmlinge dieser Verbindungen ausgenutzt werden. Inhalt und Ziel des Forschungsprojekts Unsere primären Ziele sind es, die einzelnen enzymatischen Schritte der bakteriellen Biosynthese aromatischer Polyketide (wie der Rubromycine) sowie der Tropone (Tropodithietsäure und andere schwefelhaltige Tropone) im Detail zu verstehen, welche oftmals antibiotische oder krebshemmende Aktivitäten aufweisen. Im Falle der Polyketide beinhaltet dies die Untersuchung insbesondere sauerstoffübertragender Enzyme und deren ungewöhnlicher Regulation mittels Acetyltransferasen. Bei den Troponen soll hingegen der kryptische S-Einbau aufgeklärt werden, bevor Schlüsselenzyme aus den jeweiligen Biosynthesewegen bezüglich ihrer räumlichen Struktur und ihres Reaktionsmechanismus im Detail charakterisiert werden. Dieses Wissen wird daraufhin für die Herstellung neuartiger Derivate dieser Naturstoffklassen eingesetzt, welche zudem bezüglich ihrer Bioaktivitäten untersucht werden sollen. Wissenschaftlicher und gesellschaftlicher Kontext des Forschungsprojekts Unsere Arbeit wird neue Erkenntnisse über enzymatische Reaktionen liefern, die von zentraler Bedeutung für die Herstellung komplexer mikrobieller Naturstoffe sind. Das erworbene Wissen soll als Grundlage dienen, diese Enzyme gezielt einzusetzen und abzuändern, um neuartige bioaktive Verbindungen und somit potentielle Wirkstoffkandidaten herzustellen. Simulation in pharmacy education Research Project | 2 Project MembersIt is a challenge for pharmacy universities worldwide to combine theoretical knowledge with practical skills to equip students for their future practice. Simulation - either virtual or on-site - has expanded rapidly as new technique of learning. In July 2022 and for the first time in Switzerland, a fully equipped pharmacy has been installed at the Pharmazentrum, University of Basel, for simulation purposes. Scientific research is needed to establish simulation in the curriculum. This project aims at developing scenarios from clinical / pharmaceutical cases to be used by pharmacy students in simulation. Variables for the assessment of learning progress will be determined. A comparison with digital simulation is planned. SwissPandemic&AmR-Health Ecoomy Awareness Detect (SPEARHEAD) - SP1 Research Project | 3 Project MembersFighting Antimicrobial resistance through rapid digital pandemic response Our consortium of 8 public and 4 private Swiss institutions has joined forces to address the silent pandemic of antimicrobial resistance (AMR) by launching the 'Swiss Pandemic & AMR - Health Economy Awareness Detect' (SPEARHEAD) partnership. AMR is the ability of microorganisms (like bacteria, viruses, and some parasites) to prevent antimicrobials (such as antibiotics, antivirals and antimalarials) from working against them. As a result, many treatments are becoming ineffective against infections that were previously easily treatable. SPEARHEAD will leverage lessons learnt to address the steadily worsening, silent pandemic of AMR, with potentially 10M deaths per year globally by 2050 (4 x the 2020 COVID-19 death toll) and the related economic impact on society. Specificity, selectivity and pharmacokinetics of compstatin: a comprehensive multidisciplinary analysis Research Project | 6 Project MembersThe complement system plays a major role in innate immunity as it confers immune surveillance and first-line defense against non- or altered-self entities such as microbes or apoptotic cells. Yet, misguided complement activation may trigger or contribute to severe clinical conditions or complications, including autoimmune, hemolytic, inflammatory and age-related disorders and transplant rejection (PMID) [1]. Owing to its cascade organization, involving ~50 plasma proteins, receptors and enzymes, complement provides multiple points for novel pharmacological intervention [2]. However, few complement-targeted drugs have reached the clinic, and the available options primarily target peripheral steps in cascade initiation or effector generation. For many acute-phase or multifactorial complement disorders, blocking the activation of the central complement component C3 is considered important [3]. Derivatives of compstatin, a peptidic inhibitor of C3 activation [4], are the most advanced compounds in this class, with two candidate drugs being evaluated in clinical trials. However, its narrow species-specificity for primate C3 currently restricts a broader exploration of potential benefits of C3 inhibition in various established animal models of complement disorders. Furthermore, despite considerable progress in structure optimization, some pharmacokinetic and physicochemical properties of the compstatin class remain to be improved to fully unleash its unique therapeutic potential. The main objective of this project is to understand target binding and complement inhibition by compstatin in the human system at the atomic level and identify key determinants of its narrow species specificity. We will utilize this knowledge for designing compstatin analogs that recognize non-primate C3 and, for example, inhibit mouse, rat or pig complement. Simultaneously, we will assess compstatin's target selectivity for C3 over the orthologous C4 and C5 proteins and explore options for achieving C4-, C5- or pan-specific inhibitors for research or clinical applications. Finally, we will analyze and optimize the pharmacokinetic properties of compstatin with special emphasis on solubility and bioavailability. The proposed rationalization and optimization efforts will be driven by well-established in silico simulation techniques such as molecular dynamics simulations, free energy methods, homology modeling, and post-MD analyses, supported by novel approaches based on deep learning (Prof. Markus Lill, Computational Pharmacy). Thanks to project collaborations with strong experimental groups, in silico findings will be experimentally verified by employing peptide synthesis and characterization, chemical modification and labeling, and target binding and functional assays in vitro (Prof. Daniel Ricklin, Molecular Pharmacy) as well as pre-clinical assessments of cellular permeability in vitro and in vivo (Prof. Henriette Meyer zu Schwabedissen, Biopharmacy; all at University of Basel). Our studies are expected to extend preclinical evaluation options of compstatin-based drugs in animal models and enhance their pharmacokinetic profile, thereby facilitating clinical development of this important inhibitor class. Selectivity studies with C4/C5 may provide insight into complement activation and potentially reveal novel inhibitors. Finally, atomic level insight into the structure-activity/property relationships of cyclic peptides may be used for the design of this compound type in general. [1] Ricklin, D.; Reis, E. S.; Lambris, J. D. Complement in Disease: A Defence System Turning Offensive. Nat. Rev. Nephrol. 2016, 12 (7), 383-401. https://doi.org/10.1038/nrneph.2016.70. [2] Mastellos, D.C., Ricklin, D. & Lambris, J.D. Clinical promise of next-generation complement therapeutics. Nat Rev Drug Discov 18, 707-729 (2019). https://doi.org/10.1038/s41573-019-0031-6 [3] Mastellos, D. C.; Reis, E. S.; Ricklin, D.; Smith, R. J.; Lambris, J. D. Complement C3-Targeted Therapy: Replacing Long-Held Assertions with Evidence-Based Discovery. Trends Immunol. 2017, 38 (6), 383-394. https://doi.org/10.1016/j.it.2017.03.003. [4] Mastellos, D. C.; Yancopoulou, D.; Kokkinos, P.; Huber-Lang, M.; Hajishengallis, G.; Biglarnia, A. R.; Lupu, F.; Nilsson, B.; Risitano, A. M.; Ricklin, D.; Lambris, J. D. Compstatin: A C3-Targeted Complement Inhibitor Reaching Its Prime for Bedside Intervention. Eur. J. Clin. Invest. 2015, 45 (4), 423-440. https://doi.org/10.1111/eci.12419. m-Health ⁄ smartphone apps to foster adherence to medication Research Project | 2 Project MembersMedication adherence is a prerequisite to treatment outcomes. We will develop an Smartphone application aimed at fostering adherence to medication via mobile phone technology. Patients will record intakes and self-evaluate symptoms. Pharmacists will have a central role to play in interpreting the adherence data and delivering a targeted counseling. A report will be created that includes a pharmaceutical recommendation by the pharmacists and that will be shared with the physician. Physicians will be able to adjust treatment guided by adherence reports and self-evaluation of symptoms. Interprofessionality will be fostered. Feasibility study will be preformed with short-term PPI. A study on the epidemiology of treated glaucoma in the UK Research Project | 5 Project MembersBackground: Glaucoma is a group of progressive optic neuropathies that have in common a slow progressive neurodegeneration of retinal cells and their axons and a concomitant pattern of visual loss. The biological basis of the disease is not yet fully understood, and the factors contributing to its progression are not yet fully characterised. However, intraocular pressure is the only proven treatable risk factor. Glaucoma is the second most common cause of vision loss worldwide behind cataracts, but, unlike cataracts, the vision loss associated with glaucoma is largely irreversible. Among the major types of glaucoma are open-angle (OAG), angle-closure (ACG), secondary glaucoma, and glaucoma with onset in infancy. In 2010 it was estimated that 60.5 million people suffer with OAG or ACG worldwide. These numbers are expected to reach 79.6 million by 2020, and of these, 74% will have OAG. To our knowledge, incidence rates of glaucoma have not been quantified in the UK. Objective: We therefore aim to quantify, through an observational study, the treatment rates for glaucoma and intraocular hypertension (IOH) in the U.K. and compare demographic characteristics, comorbidities (e.g. obesity, diabetes, others), and lifestyle factors (smoking, alcohol consumption) between treated patients with and untreated (i.e., glaucoma-free) controls. Furthermore, we plan to conduct one ore more drug safety studies, using a case-control design, on the risk of glaucoma after exposure to certain drugs of interest. Additionally, we plan to assess the association between other chronic conditions and the risk of glaucoma. Methods: we will assess standardized treatement rates and perform stratified analyses for age, sex and region of the UK. We will further describe and compare pateint charcteristics with the general population. For the study of potential associations with glaucom we will use a case-control design and perform conditional logistic regression analyes. 12 12
Design of antimicrobial peptides through active learning Research Project | 2 Project MembersNo Description available
Psilocybin-induced synaptic plasticity: circuit mechanisms underlying the antidepressant potential of hallucinogens Research Project | 1 Project MembersPsilocybin induces hallucinations through its active metabolite psilocin, which acts as serotonin (5-HT) 2A receptor agonist. Although classified as drugs of abuse, psilocybin and other hallucinogens may be clinically used for several psychiatric disorders, including major depressive disorder. Preliminary clinical studies advocate administering single doses of psilocybin intermittently, based on the observation that a single dose induces long-lasting therapeutic effects. Neuronal plasticity may underlie these long-lasting effects. In humans, psilocybin acutely increases the activity of the prefrontal cortex, likely by facilitating thalamocortical signaling. This coincides with the localization of 5-HT 2A receptors, which are expressed in frontal cortex pyramidal cells postsynaptically and putatively in thalamic afferents on the presynaptic site. In rodent brain slices, 5-HT and various hallucinogens acutely increase synaptic strength of glutamate afferents onto cortical pyramidal neurons. Specific neuronal circuits and synapses that may be persistently changed after psilocybin have not been identified and we lack proof of causality for antidepressant efficacy. We will therefore examine synaptic plasticity in defined neuronal circuits as a mechanism underlying psilocybin's effect on anhedonia, a key symptom of depression. Further, we will investigate a simple, translational strategy to refine psilocybin pharmacotherapy. Akin to classical conditioning, pairing psilocybin treatment with a cue may allow recalling the therapeutic benefits through cue exposure when the initial drug effect wears off. This strategy could enhance the efficacy of psilocybin treatment sessions. This project builds on the hypotheses that psilocybin induces long-lasting forms of plasticity at thalamocortical synapses, which underlie its antidepressant-like effects, and that the potential therapeutic effect can be recalled through exposure to a drug-associated cue. We aim to identify neuronal circuits involved in psilocybin-induced long-term synaptic plasticity, establish psilocybin efficacy for antidepressant-like effects and elucidate the underlying mechanism, and provide evidence for recall of psilocybin effects through drug-cue conditioning that may be clinically translated. Optogenetics and whole-cell patch-clamp slice recordings will be used for celltype- and circuit-specific observations and manipulations. Behavioral testing of anhedonia in an anxiogenic environment will be applied, as this can report the antidepressant potential of a drug. This research will reveal the clinically relevant mode of action of psilocybin and provide blueprints for improved treatment strategies such as the supportive application of conditioned drug cues.
ToxOligo2 - Toxicological properties of oligomers present in food contact materials Research Project | 6 Project MembersToxOligo addresses an important knowledge gap by evaluating toxicological properties of oligomers released from polymers as food contact materials (FCM). The formation and presence of oligomers is inevitable in such FCM. Despite known migration into food, these substances are toxicologically poorly characterized, preventing adequate risk assessment. The ongoing project phase allowed essential new insights into available information on oligomers from all polymeric FCM. A pilot study on PET helped to design an optimized strategy and workflow to address this task. Information on physicochemical, ADME and toxicological properties was collected using computational methods. In a second project phase, a collection of oligomers from all other materials will be made based on the obtained information. The focus will be on bioactivity assessment of these substances. Hazard profiles will be established using various in vitro assays to assess general toxicity, cellular stress pathways, macrophage activation and endocrine effects. These studies aim at assessing the level of concern of such substances and providing recommendations for prioritization of future toxicological testing.
P3S: Physicians and pharmacists together improving patient's medication safety Research Project | 4 Project MembersArzneimittel sind wichtig für die erfolgreiche Behandlung von vielen Krankheiten. Sie können aber auch zu Problemen führen, besonders wenn mehrere Arzneimittel gleichzeitig und über längere Zeit verwendet werden. Arzneimittelbezogene Probleme (DRP) wie Medikationsfehler, unerwünschte Arzneimittelwirkungen (UAW) und Interaktionsprobleme sind häufig und habe oftmals unnötige, medizinisch gefährliche und teure Folgen. Interventionen zur Behebung von DRP wie ein systematischer Medikationsabgleich und Medikationsanalysen erfolgen, wenn überhaupt, häufig erst reaktiv bei einer Spitaleinweisung, obwohl 80-90% der Gesundheitsbetreuung im ambulanten Setting stattfinden. Deshalb ist es wichtig, regelmässig das Risiko für arzneimittelbezogene Probleme zu überprüfen. Dies geschieht am besten dort, wo Menschen mit Medikamenten am meisten Kontakt zu medizinischen Fachpersonen haben: Bei den Hausärztinnen und Hausärzten und in den Apotheken. Ein integrierter, strukturierter und interprofessioneller Prozess zur Therapieoptimierung bei Patienten mit hohem Risiko für DRP schafft Transparenz und in Anbetracht des Fachkräftemangels eine gleichbleibend hohe Behandlungsqualität für Patienten, Sicherheit für die Behandler und Kostenersparnisse. Bisher existieren in der Schweiz jedoch keine systematischen Ansätze für die interprofessionelle Zusammenarbeit zwischen Ärzten und Apothekern zur Optimierung der Arzneimittelsicherheit. Das Projekt «Physicians and pharmacists together improving patient's medication safety» (P 3 S) will die Zusammenarbeit zwischen diesen Fachpersonen verbessern, um arzneimittelbezogene Probleme zu verhindern. Dafür werden Risiken für arzneimittelbezogene Probleme durch eine regelmässige Abklärung in der Hausarztpraxis frühzeitig identifiziert. Bei einem erhöhten Risiko können aufgrund einer Medikationsanalyse in der Apotheke anschliessend gezielte Massnahmen zur Therapieoptimierung ergriffen werden. Die identifizierten Risiken, potenzielle und manifeste DRP sowie Optimierungsvorschläge und umgesetzte Massnahmen werden strukturiert erfasst und stehen als Basis für die kontinuierliche Verbesserung der Arzneimittelsicherheit zur Verfügung. Um eine nachhaltige Verbesserung zu erreichen, werden die Abläufe und Hilfsmittel im Rahmen des Projekts in enger Zusammenarbeit mit den Patienten und beteiligten Fachpersonen entwickelt und getestet. Anschliessend wird untersucht, wie die Abläufe erfolgreich in die Praxis an unterschiedlichen Standorten integriert werden können. Schlussendlich werden in einer Studie die Wirkung und Umsetzung wissenschaftlich geprüft. Das Projekt wird von der Eidgenössischen Qualitätskommission finanziell unterstützt und dauert von 1.1.2023 bis 31.12.2026.
Biosynthesis, Enzymology and Biotechnology of Bacterial Aromatic Polyketide and Tropone Natural Products Research Project | 1 Project MembersLead Bakterielle aromatische Polyketide und Tropone sind Naturstoffe mit vielseitigen Bioaktivitäten, welche sowohl essentielle Rollen in der Natur einnehmen (beispielsweise im Rahmen symbiotischer Interaktionen), als auch potentielle Leitstrukturen für die Entwicklung von Wirkstoffkandidaten für medizinische Anwendungen sind. Die Biosynthese dieser Verbindungen ist oftmals nur unzulänglich beschrieben, insbesondere bezüglich der Bildung der teils komplexen Pharmakophore, sowie des Einbaus von sauerstoff- oder schwefelhaltigen funktionellen Gruppen. Ein besseres Verständnis über diese Prozesse könnte beispielsweise für die Herstellung neuartiger bioaktiver Abkömmlinge dieser Verbindungen ausgenutzt werden. Inhalt und Ziel des Forschungsprojekts Unsere primären Ziele sind es, die einzelnen enzymatischen Schritte der bakteriellen Biosynthese aromatischer Polyketide (wie der Rubromycine) sowie der Tropone (Tropodithietsäure und andere schwefelhaltige Tropone) im Detail zu verstehen, welche oftmals antibiotische oder krebshemmende Aktivitäten aufweisen. Im Falle der Polyketide beinhaltet dies die Untersuchung insbesondere sauerstoffübertragender Enzyme und deren ungewöhnlicher Regulation mittels Acetyltransferasen. Bei den Troponen soll hingegen der kryptische S-Einbau aufgeklärt werden, bevor Schlüsselenzyme aus den jeweiligen Biosynthesewegen bezüglich ihrer räumlichen Struktur und ihres Reaktionsmechanismus im Detail charakterisiert werden. Dieses Wissen wird daraufhin für die Herstellung neuartiger Derivate dieser Naturstoffklassen eingesetzt, welche zudem bezüglich ihrer Bioaktivitäten untersucht werden sollen. Wissenschaftlicher und gesellschaftlicher Kontext des Forschungsprojekts Unsere Arbeit wird neue Erkenntnisse über enzymatische Reaktionen liefern, die von zentraler Bedeutung für die Herstellung komplexer mikrobieller Naturstoffe sind. Das erworbene Wissen soll als Grundlage dienen, diese Enzyme gezielt einzusetzen und abzuändern, um neuartige bioaktive Verbindungen und somit potentielle Wirkstoffkandidaten herzustellen.
Simulation in pharmacy education Research Project | 2 Project MembersIt is a challenge for pharmacy universities worldwide to combine theoretical knowledge with practical skills to equip students for their future practice. Simulation - either virtual or on-site - has expanded rapidly as new technique of learning. In July 2022 and for the first time in Switzerland, a fully equipped pharmacy has been installed at the Pharmazentrum, University of Basel, for simulation purposes. Scientific research is needed to establish simulation in the curriculum. This project aims at developing scenarios from clinical / pharmaceutical cases to be used by pharmacy students in simulation. Variables for the assessment of learning progress will be determined. A comparison with digital simulation is planned.
SwissPandemic&AmR-Health Ecoomy Awareness Detect (SPEARHEAD) - SP1 Research Project | 3 Project MembersFighting Antimicrobial resistance through rapid digital pandemic response Our consortium of 8 public and 4 private Swiss institutions has joined forces to address the silent pandemic of antimicrobial resistance (AMR) by launching the 'Swiss Pandemic & AMR - Health Economy Awareness Detect' (SPEARHEAD) partnership. AMR is the ability of microorganisms (like bacteria, viruses, and some parasites) to prevent antimicrobials (such as antibiotics, antivirals and antimalarials) from working against them. As a result, many treatments are becoming ineffective against infections that were previously easily treatable. SPEARHEAD will leverage lessons learnt to address the steadily worsening, silent pandemic of AMR, with potentially 10M deaths per year globally by 2050 (4 x the 2020 COVID-19 death toll) and the related economic impact on society.
Specificity, selectivity and pharmacokinetics of compstatin: a comprehensive multidisciplinary analysis Research Project | 6 Project MembersThe complement system plays a major role in innate immunity as it confers immune surveillance and first-line defense against non- or altered-self entities such as microbes or apoptotic cells. Yet, misguided complement activation may trigger or contribute to severe clinical conditions or complications, including autoimmune, hemolytic, inflammatory and age-related disorders and transplant rejection (PMID) [1]. Owing to its cascade organization, involving ~50 plasma proteins, receptors and enzymes, complement provides multiple points for novel pharmacological intervention [2]. However, few complement-targeted drugs have reached the clinic, and the available options primarily target peripheral steps in cascade initiation or effector generation. For many acute-phase or multifactorial complement disorders, blocking the activation of the central complement component C3 is considered important [3]. Derivatives of compstatin, a peptidic inhibitor of C3 activation [4], are the most advanced compounds in this class, with two candidate drugs being evaluated in clinical trials. However, its narrow species-specificity for primate C3 currently restricts a broader exploration of potential benefits of C3 inhibition in various established animal models of complement disorders. Furthermore, despite considerable progress in structure optimization, some pharmacokinetic and physicochemical properties of the compstatin class remain to be improved to fully unleash its unique therapeutic potential. The main objective of this project is to understand target binding and complement inhibition by compstatin in the human system at the atomic level and identify key determinants of its narrow species specificity. We will utilize this knowledge for designing compstatin analogs that recognize non-primate C3 and, for example, inhibit mouse, rat or pig complement. Simultaneously, we will assess compstatin's target selectivity for C3 over the orthologous C4 and C5 proteins and explore options for achieving C4-, C5- or pan-specific inhibitors for research or clinical applications. Finally, we will analyze and optimize the pharmacokinetic properties of compstatin with special emphasis on solubility and bioavailability. The proposed rationalization and optimization efforts will be driven by well-established in silico simulation techniques such as molecular dynamics simulations, free energy methods, homology modeling, and post-MD analyses, supported by novel approaches based on deep learning (Prof. Markus Lill, Computational Pharmacy). Thanks to project collaborations with strong experimental groups, in silico findings will be experimentally verified by employing peptide synthesis and characterization, chemical modification and labeling, and target binding and functional assays in vitro (Prof. Daniel Ricklin, Molecular Pharmacy) as well as pre-clinical assessments of cellular permeability in vitro and in vivo (Prof. Henriette Meyer zu Schwabedissen, Biopharmacy; all at University of Basel). Our studies are expected to extend preclinical evaluation options of compstatin-based drugs in animal models and enhance their pharmacokinetic profile, thereby facilitating clinical development of this important inhibitor class. Selectivity studies with C4/C5 may provide insight into complement activation and potentially reveal novel inhibitors. Finally, atomic level insight into the structure-activity/property relationships of cyclic peptides may be used for the design of this compound type in general. [1] Ricklin, D.; Reis, E. S.; Lambris, J. D. Complement in Disease: A Defence System Turning Offensive. Nat. Rev. Nephrol. 2016, 12 (7), 383-401. https://doi.org/10.1038/nrneph.2016.70. [2] Mastellos, D.C., Ricklin, D. & Lambris, J.D. Clinical promise of next-generation complement therapeutics. Nat Rev Drug Discov 18, 707-729 (2019). https://doi.org/10.1038/s41573-019-0031-6 [3] Mastellos, D. C.; Reis, E. S.; Ricklin, D.; Smith, R. J.; Lambris, J. D. Complement C3-Targeted Therapy: Replacing Long-Held Assertions with Evidence-Based Discovery. Trends Immunol. 2017, 38 (6), 383-394. https://doi.org/10.1016/j.it.2017.03.003. [4] Mastellos, D. C.; Yancopoulou, D.; Kokkinos, P.; Huber-Lang, M.; Hajishengallis, G.; Biglarnia, A. R.; Lupu, F.; Nilsson, B.; Risitano, A. M.; Ricklin, D.; Lambris, J. D. Compstatin: A C3-Targeted Complement Inhibitor Reaching Its Prime for Bedside Intervention. Eur. J. Clin. Invest. 2015, 45 (4), 423-440. https://doi.org/10.1111/eci.12419.
m-Health ⁄ smartphone apps to foster adherence to medication Research Project | 2 Project MembersMedication adherence is a prerequisite to treatment outcomes. We will develop an Smartphone application aimed at fostering adherence to medication via mobile phone technology. Patients will record intakes and self-evaluate symptoms. Pharmacists will have a central role to play in interpreting the adherence data and delivering a targeted counseling. A report will be created that includes a pharmaceutical recommendation by the pharmacists and that will be shared with the physician. Physicians will be able to adjust treatment guided by adherence reports and self-evaluation of symptoms. Interprofessionality will be fostered. Feasibility study will be preformed with short-term PPI.
A study on the epidemiology of treated glaucoma in the UK Research Project | 5 Project MembersBackground: Glaucoma is a group of progressive optic neuropathies that have in common a slow progressive neurodegeneration of retinal cells and their axons and a concomitant pattern of visual loss. The biological basis of the disease is not yet fully understood, and the factors contributing to its progression are not yet fully characterised. However, intraocular pressure is the only proven treatable risk factor. Glaucoma is the second most common cause of vision loss worldwide behind cataracts, but, unlike cataracts, the vision loss associated with glaucoma is largely irreversible. Among the major types of glaucoma are open-angle (OAG), angle-closure (ACG), secondary glaucoma, and glaucoma with onset in infancy. In 2010 it was estimated that 60.5 million people suffer with OAG or ACG worldwide. These numbers are expected to reach 79.6 million by 2020, and of these, 74% will have OAG. To our knowledge, incidence rates of glaucoma have not been quantified in the UK. Objective: We therefore aim to quantify, through an observational study, the treatment rates for glaucoma and intraocular hypertension (IOH) in the U.K. and compare demographic characteristics, comorbidities (e.g. obesity, diabetes, others), and lifestyle factors (smoking, alcohol consumption) between treated patients with and untreated (i.e., glaucoma-free) controls. Furthermore, we plan to conduct one ore more drug safety studies, using a case-control design, on the risk of glaucoma after exposure to certain drugs of interest. Additionally, we plan to assess the association between other chronic conditions and the risk of glaucoma. Methods: we will assess standardized treatement rates and perform stratified analyses for age, sex and region of the UK. We will further describe and compare pateint charcteristics with the general population. For the study of potential associations with glaucom we will use a case-control design and perform conditional logistic regression analyes.
