{"title":"Hits and misses with animal models of narcolepsy and the implications for drug discovery.","authors":"Ramakrishna Nirogi, Pradeep Jayarajan, Vijay Benade, Renny Abraham, Vinod Kumar Goyal","doi":"10.1080/17460441.2024.2354293","DOIUrl":"10.1080/17460441.2024.2354293","url":null,"abstract":"<p><strong>Introduction: </strong>Narcolepsy is a chronic and rare neurological disorder characterized by disordered sleep. Based on animal models and further research in humans, the dysfunctional orexin system was identified as a contributing factor to the pathophysiology of narcolepsy. Animal models played a larger role in the discovery of some of the pharmacological agents with established benefit/risk profiles.</p><p><strong>Areas covered: </strong>In this review, the authors examine the phenotypes observed in animal models of narcolepsy and the characteristics of clinically used pharmacological agents in these animal models. Additionally, the authors compare the effects of clinically used pharmacological agents on the phenotypes in animal models with those observed in narcolepsy patients.</p><p><strong>Expert opinion: </strong>Research in canine and mouse models have linked narcolepsy to the O×R2mutation and orexin deficiency, leading to new diagnostic criteria and a drug development focus. Advancements in pharmacological therapies have significantly improved narcolepsy management, with insights from both clinical experience and from animal models having led to new treatments such as low sodium oxybate and solriamfetol. However, challenges persist in addressing symptoms beyond excessive daytime sleepiness and cataplexy, highlighting the need for further research, including the development of diurnal animal models to enhance understanding and treatment options for narcolepsy.</p>","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140920935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"What is the plausibility that all drugs will be designed by computers by the end of the decade?","authors":"José L Medina-Franco, Edgar López-López","doi":"10.1080/17460441.2024.2331734","DOIUrl":"10.1080/17460441.2024.2331734","url":null,"abstract":"","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.3,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140157875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marc Rogers, Alison Obergrussberger, Artem Kondratskyi, Niels Fertig
{"title":"Using automated patch clamp electrophysiology platforms in ion channel drug discovery: an industry perspective.","authors":"Marc Rogers, Alison Obergrussberger, Artem Kondratskyi, Niels Fertig","doi":"10.1080/17460441.2024.2329104","DOIUrl":"10.1080/17460441.2024.2329104","url":null,"abstract":"<p><strong>Introduction: </strong>Automated patch clamp (APC) is now well established as a mature technology for ion channel drug discovery in academia, biotech and pharma companies, and in contract research organizations (CRO), for a variety of applications including channelopathy research, compound screening, target validation and cardiac safety testing.</p><p><strong>Areas covered: </strong>Ion channels are an important class of drugged and approved drug targets. The authors present a review of the current state of ion channel drug discovery along with new and exciting developments in ion channel research involving APC. This includes topics such as native and iPSC-derived cells in ion channel drug discovery, channelopathy research, organellar and biologics in ion channel drug discovery.</p><p><strong>Expert opinion: </strong>It is our belief that APC will continue to play a critical role in ion channel drug discovery, not only in 'classical' hit screening, target validation and cardiac safety testing, but extending these applications to include high throughput organellar recordings and optogenetics. In this way, with advancements in APC capabilities and applications, together with high resolution cryo-EM structures, ion channel drug discovery will be re-invigorated, leading to a growing list of ion channel ligands in clinical development.</p>","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.3,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140119220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Identification of the abnormalities in astrocytic functions as potential drug targets for neurodegenerative disease.","authors":"Valtteri Syvänen, Jari Koistinaho, Šárka Lehtonen","doi":"10.1080/17460441.2024.2322988","DOIUrl":"10.1080/17460441.2024.2322988","url":null,"abstract":"<p><strong>Introduction: </strong>Historically, astrocytes were seen primarily as a supportive cell population within the brain; with neurodegenerative disease research focusing exclusively on malfunctioning neurons. However, astrocytes perform numerous tasks that are essential for maintenance of the central nervous system`s complex processes. Disruption of these functions can have negative consequences; hence, it is unsurprising to observe a growing amount of evidence for the essential role of astrocytes in the development and progression of neurodegenerative diseases. Targeting astrocytic functions may serve as a potential disease-modifying drug therapy in the future.</p><p><strong>Areas covered: </strong>The present review emphasizes the key astrocytic functions associated with neurodegenerative diseases and explores the possibility of pharmaceutical interventions to modify these processes. In addition, the authors provide an overview of current advancement in this field by including studies of possible drug candidates.</p><p><strong>Expert opinion: </strong>Glial research has experienced a significant renaissance in the last quarter-century. Understanding how disease pathologies modify or are caused by astrocyte functions is crucial when developing treatments for brain diseases. Future research will focus on building advanced models that can more precisely correlate to the state in the human brain, with the goal of routinely testing therapies in these models.</p>","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.3,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139971487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stefano Romussi, Sebastián Giunti, Natalia Andersen, María José De Rosa
{"title":"<i>C. elegans</i>: a prominent platform for modeling and drug screening in neurological disorders.","authors":"Stefano Romussi, Sebastián Giunti, Natalia Andersen, María José De Rosa","doi":"10.1080/17460441.2024.2329103","DOIUrl":"10.1080/17460441.2024.2329103","url":null,"abstract":"<p><strong>Introduction: </strong>Human neurodevelopmental and neurodegenerative diseases (NDevDs and NDegDs, respectively) encompass a broad spectrum of disorders affecting the nervous system with an increasing incidence. In this context, the nematode <i>C. elegans</i>, has emerged as a benchmark model for biological research, especially in the field of neuroscience.</p><p><strong>Areas covered: </strong>The authors highlight the numerous advantages of this tiny worm as a model for exploring nervous system pathologies and as a platform for drug discovery. There is a particular focus given to describing the existing models of <i>C.</i> <i>elegans</i> for the study of NDevDs and NDegDs. Specifically, the authors underscore their strong applicability in preclinical drug development. Furthermore, they place particular emphasis on detailing the common techniques employed to explore the nervous system in both healthy and diseased states.</p><p><strong>Expert opinion: </strong>Drug discovery constitutes a long and expensive process. The incorporation of invertebrate models, such as <i>C.</i> <i>elegans</i>, stands as an exemplary strategy for mitigating costs and expediting timelines. The utilization of <i>C.</i> <i>elegans</i> as a platform to replicate nervous system pathologies and conduct high-throughput automated assays in the initial phases of drug discovery is pivotal for rendering therapeutic options more attainable and cost-effective.</p>","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.3,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140174135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Madia Lozupone, Vittorio Dibello, Rodolfo Sardone, Fabio Castellana, Roberta Zupo, Luisa Lampignano, Ilaria Bortone, Roberta Stallone, Mario Altamura, Antonello Bellomo, Antonio Daniele, Vincenzo Solfrizzi, Francesco Panza
{"title":"Lessons learned from the failure of solanezumab as a prospective treatment strategy for Alzheimer’s disease","authors":"Madia Lozupone, Vittorio Dibello, Rodolfo Sardone, Fabio Castellana, Roberta Zupo, Luisa Lampignano, Ilaria Bortone, Roberta Stallone, Mario Altamura, Antonello Bellomo, Antonio Daniele, Vincenzo Solfrizzi, Francesco Panza","doi":"10.1080/17460441.2024.2348142","DOIUrl":"https://doi.org/10.1080/17460441.2024.2348142","url":null,"abstract":"In the last decade, the efforts conducted for discovering Alzheimer’s Disease (AD) treatments targeting the best-known pathogenic factors [amyloid–β (Aβ), tau protein, and neuroinflammation] were m...","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.3,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140839780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ivette A. Nuñez, Anya Crane, Ian Crozier, Gabriella Worwa, Jens H. Kuhn
{"title":"Treatment of highly virulent mammarenavirus infections—status quo and future directions","authors":"Ivette A. Nuñez, Anya Crane, Ian Crozier, Gabriella Worwa, Jens H. Kuhn","doi":"10.1080/17460441.2024.2340494","DOIUrl":"https://doi.org/10.1080/17460441.2024.2340494","url":null,"abstract":"Mammarenaviruses are negative-sense bisegmented enveloped RNA viruses that are endemic in Africa, the Americas, and Europe. Several are highly virulent, causing acute human diseases associated with...","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.3,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140587251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Omega-3 polyunsaturated fatty acid derived lipid mediators: a comprehensive update on their application in anti-cancer drug discovery","authors":"Michael Murray","doi":"10.1080/17460441.2024.2340493","DOIUrl":"https://doi.org/10.1080/17460441.2024.2340493","url":null,"abstract":"ω-3 Polyunsaturated fatty acids (PUFAs) have a range of health benefits, including anticancer activity, and are converted to lipid mediators that could be adapted into pharmacological strategies. H...","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.3,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140579421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Izabela Lepiarz-Raba, Taufik Hidayat, Anthony J. Hannan, Ali Jawaid
{"title":"Potential Alzheimer’s disease drug targets identified through microglial biology research","authors":"Izabela Lepiarz-Raba, Taufik Hidayat, Anthony J. Hannan, Ali Jawaid","doi":"10.1080/17460441.2024.2335210","DOIUrl":"https://doi.org/10.1080/17460441.2024.2335210","url":null,"abstract":"Microglia, the primary immune cells in the brain, play multifaceted roles in Alzheimer’s disease (AD). Microglia can potentially mitigate the pathological progression of AD by clearing amyloid beta...","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.3,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140580133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The preclinical discovery and clinical development of ciltacabtagene autoleucel (Cilta-cel) for the treatment of multiple myeloma.","authors":"Irene Strassl, Klaus Podar","doi":"10.1080/17460441.2024.2319672","DOIUrl":"10.1080/17460441.2024.2319672","url":null,"abstract":"<p><strong>Introduction: </strong>Despite remarkable therapeutic advances over the last two decades, which have resulted in dramatic improvements in patient survival, multiple myeloma (MM) is still considered an incurable disease. Therefore, there is a high need for new treatment strategies. Genetically engineered/redirected chimeric antigen receptor (CAR) T cells may represent the most compelling modality of immunotherapy for cancer treatment in general, and MM in particular. Indeed, unprecedented response rates have led to the recent approvals of the first two BCMA-targeted CAR T cell products idecabtagene-vicleucel ('Ide-cel') and ciltacabtagene-autoleucel ('Cilta-Cel') for the treatment of heavily pretreated MM patients. In addition, both are emerging as a new standard-of-care also in earlier lines of therapy.</p><p><strong>Areas covered: </strong>This article briefly reviews the history of the preclinical development of CAR T cells, with a particular focus on Cilta-cel. Moreover, it summarizes the newest clinical data on Cilta-cel and discusses strategies to further improve its activity and reduce its toxicity.</p><p><strong>Expert opinion: </strong>Modern next-generation immunotherapy is continuously transforming the MM treatment landscape. Despite several caveats of CAR T cell therapy, including its toxicity, costs, and limited access, prolonged disease-free survival and potential cure of MM are finally within reach.</p>","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.3,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139899609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}