Pub Date : 2024-07-22DOI: 10.1038/s41573-024-00981-w
Pavel Klein, Rafal M. Kaminski, Matthias Koepp, Wolfgang Löscher
Epilepsy is a common brain disorder, characterized by spontaneous recurrent seizures, with associated neuropsychiatric and cognitive comorbidities and increased mortality. Although people at risk can often be identified, interventions to prevent the development of the disorder are not available. Moreover, in at least 30% of patients, epilepsy cannot be controlled by current antiseizure medications (ASMs). As a result of considerable progress in epilepsy genetics and the development of novel disease models, drug screening technologies and innovative therapeutic modalities over the past 10 years, more than 200 novel epilepsy therapies are currently in the preclinical or clinical pipeline, including many treatments that act by new mechanisms. Assisted by diagnostic and predictive biomarkers, the treatment of epilepsy is undergoing paradigm shifts from symptom-only ASMs to disease prevention, and from broad trial-and-error treatments for seizures in general to mechanism-based treatments for specific epilepsy syndromes. In this Review, we assess recent progress in ASM development and outline future directions for the development of new therapies for the treatment and prevention of epilepsy. Epilepsy is a common and debilitating brain disorder for which current antiseizure medications (ASMs) provide inadequate efficacy in around 30% of patients. In their Review, Pavel Klein and colleagues survey the diverse ASM pipeline, including new approaches to target specific epilepsy syndromes, and discuss strategies for disease prevention.
{"title":"New epilepsy therapies in development","authors":"Pavel Klein, Rafal M. Kaminski, Matthias Koepp, Wolfgang Löscher","doi":"10.1038/s41573-024-00981-w","DOIUrl":"10.1038/s41573-024-00981-w","url":null,"abstract":"Epilepsy is a common brain disorder, characterized by spontaneous recurrent seizures, with associated neuropsychiatric and cognitive comorbidities and increased mortality. Although people at risk can often be identified, interventions to prevent the development of the disorder are not available. Moreover, in at least 30% of patients, epilepsy cannot be controlled by current antiseizure medications (ASMs). As a result of considerable progress in epilepsy genetics and the development of novel disease models, drug screening technologies and innovative therapeutic modalities over the past 10 years, more than 200 novel epilepsy therapies are currently in the preclinical or clinical pipeline, including many treatments that act by new mechanisms. Assisted by diagnostic and predictive biomarkers, the treatment of epilepsy is undergoing paradigm shifts from symptom-only ASMs to disease prevention, and from broad trial-and-error treatments for seizures in general to mechanism-based treatments for specific epilepsy syndromes. In this Review, we assess recent progress in ASM development and outline future directions for the development of new therapies for the treatment and prevention of epilepsy. Epilepsy is a common and debilitating brain disorder for which current antiseizure medications (ASMs) provide inadequate efficacy in around 30% of patients. In their Review, Pavel Klein and colleagues survey the diverse ASM pipeline, including new approaches to target specific epilepsy syndromes, and discuss strategies for disease prevention.","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":null,"pages":null},"PeriodicalIF":122.7,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-22DOI: 10.1038/s41573-024-01016-0
Francisco Ramírez-Valle, Joseph C. Maranville, Sophie Roy, Robert M. Plenge
{"title":"Author Correction: Sequential immunotherapy: towards cures for autoimmunity","authors":"Francisco Ramírez-Valle, Joseph C. Maranville, Sophie Roy, Robert M. Plenge","doi":"10.1038/s41573-024-01016-0","DOIUrl":"10.1038/s41573-024-01016-0","url":null,"abstract":"","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":null,"pages":null},"PeriodicalIF":122.7,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41573-024-01016-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-18DOI: 10.1038/d41573-024-00107-2
Gunnar Esiason, Angela Pontius, Luke Gelinas
{"title":"Show them the money: a multi-stakeholder perspective on reforming clinical trial participant compensation.","authors":"Gunnar Esiason, Angela Pontius, Luke Gelinas","doi":"10.1038/d41573-024-00107-2","DOIUrl":"https://doi.org/10.1038/d41573-024-00107-2","url":null,"abstract":"","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":null,"pages":null},"PeriodicalIF":122.7,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141724031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-16DOI: 10.1038/s41573-024-00978-5
Hayden A. Malone, Charles W. M. Roberts
Large-scale cancer genome sequencing studies have revealed that chromatin regulators are frequently mutated in cancer. In particular, more than 20% of cancers harbour mutations in genes that encode subunits of SWI/SNF (BAF) chromatin remodelling complexes. Additional links of SWI/SNF complexes to disease have emerged with the findings that some oncogenes drive transformation by co-opting SWI/SNF function and that germline mutations in select SWI/SNF subunits are the basis of several neurodevelopmental disorders. Other chromatin remodellers, including members of the ISWI, CHD and INO80/SWR complexes, have also been linked to cancer and developmental disorders. Consequently, therapeutic manipulation of SWI/SNF and other remodelling complexes has become of great interest, and drugs that target SWI/SNF subunits have entered clinical trials. Genome-wide perturbation screens in cancer cell lines with SWI/SNF mutations have identified additional synthetic lethal targets and led to further compounds in clinical trials, including one that has progressed to FDA approval. Here, we review the progress in understanding the structure and function of SWI/SNF and other chromatin remodelling complexes, mechanisms by which SWI/SNF mutations cause cancer and neurological diseases, vulnerabilities that arise because of these mutations and efforts to target SWI/SNF complexes and synthetic lethal targets for therapeutic benefit. Mutations in genes that encode subunits of the SWI/SNF chromatin remodelling complexes are found in more than 20% of cancers as well as in certain neurodevelopmental disorders. This Review discusses mechanisms by which SWI/SNF mutations lead to disease and the strategies to target SWI/SNF complexes and synthetic lethal targets for therapeutic benefit.
{"title":"Chromatin remodellers as therapeutic targets","authors":"Hayden A. Malone, Charles W. M. Roberts","doi":"10.1038/s41573-024-00978-5","DOIUrl":"10.1038/s41573-024-00978-5","url":null,"abstract":"Large-scale cancer genome sequencing studies have revealed that chromatin regulators are frequently mutated in cancer. In particular, more than 20% of cancers harbour mutations in genes that encode subunits of SWI/SNF (BAF) chromatin remodelling complexes. Additional links of SWI/SNF complexes to disease have emerged with the findings that some oncogenes drive transformation by co-opting SWI/SNF function and that germline mutations in select SWI/SNF subunits are the basis of several neurodevelopmental disorders. Other chromatin remodellers, including members of the ISWI, CHD and INO80/SWR complexes, have also been linked to cancer and developmental disorders. Consequently, therapeutic manipulation of SWI/SNF and other remodelling complexes has become of great interest, and drugs that target SWI/SNF subunits have entered clinical trials. Genome-wide perturbation screens in cancer cell lines with SWI/SNF mutations have identified additional synthetic lethal targets and led to further compounds in clinical trials, including one that has progressed to FDA approval. Here, we review the progress in understanding the structure and function of SWI/SNF and other chromatin remodelling complexes, mechanisms by which SWI/SNF mutations cause cancer and neurological diseases, vulnerabilities that arise because of these mutations and efforts to target SWI/SNF complexes and synthetic lethal targets for therapeutic benefit. Mutations in genes that encode subunits of the SWI/SNF chromatin remodelling complexes are found in more than 20% of cancers as well as in certain neurodevelopmental disorders. This Review discusses mechanisms by which SWI/SNF mutations lead to disease and the strategies to target SWI/SNF complexes and synthetic lethal targets for therapeutic benefit.","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":null,"pages":null},"PeriodicalIF":122.7,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141625037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-15DOI: 10.1038/d41573-024-00118-z
Paul Verdin
{"title":"FDA new drug approvals in Q2 2024","authors":"Paul Verdin","doi":"10.1038/d41573-024-00118-z","DOIUrl":"10.1038/d41573-024-00118-z","url":null,"abstract":"","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":null,"pages":null},"PeriodicalIF":122.7,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141618333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-15DOI: 10.1038/d41573-024-00104-5
Najat S. Khan, Thomas Senderovitz, James Weatherall, Janice Branson, Benedikt Egersdoerfer, Eric Genevois-Marlin, Sai Jasti, Mustaqhusain Kazi, Ranjit Kumble, Patrick Loerch, Justine Rochon, Venkat Sethuraman, Matt Studney, Xiaoying Wu, Ryan Copping, Priya Chandran, Madura Jayatunga, Dhruv Jayanth, Christoph Meier
The DISRUPT-DS roundtable, which brings together data science leaders from large pharmaceutical companies, aims to be a forum for sharing experiences and networking, for shaping industry-level topics and for amplifying the role of data science across pharmaceutical R&D. The DISRUPT-DS roundtable, which brings together data science leaders from large pharmaceutical companies, aims to be a forum for sharing experiences and networking, for shaping industry-level topics and for amplifying the role of data science across pharmaceutical R&D.
{"title":"Data science in pharmaceutical R&D: the DISRUPT-DS industry roundtable","authors":"Najat S. Khan, \u0000 Thomas Senderovitz, \u0000 James Weatherall, \u0000 Janice Branson, \u0000 Benedikt Egersdoerfer, \u0000 Eric Genevois-Marlin, \u0000 Sai Jasti, \u0000 Mustaqhusain Kazi, \u0000 Ranjit Kumble, \u0000 Patrick Loerch, \u0000 Justine Rochon, \u0000 Venkat Sethuraman, \u0000 Matt Studney, \u0000 Xiaoying Wu, \u0000 Ryan Copping, \u0000 Priya Chandran, \u0000 Madura Jayatunga, \u0000 Dhruv Jayanth, \u0000 Christoph Meier","doi":"10.1038/d41573-024-00104-5","DOIUrl":"10.1038/d41573-024-00104-5","url":null,"abstract":"The DISRUPT-DS roundtable, which brings together data science leaders from large pharmaceutical companies, aims to be a forum for sharing experiences and networking, for shaping industry-level topics and for amplifying the role of data science across pharmaceutical R&D. The DISRUPT-DS roundtable, which brings together data science leaders from large pharmaceutical companies, aims to be a forum for sharing experiences and networking, for shaping industry-level topics and for amplifying the role of data science across pharmaceutical R&D.","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":null,"pages":null},"PeriodicalIF":122.7,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141618193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-10DOI: 10.1038/d41573-024-00117-0
M. Teresa Villanueva
{"title":"A rush of CRISPR to the lungs","authors":"M. Teresa Villanueva","doi":"10.1038/d41573-024-00117-0","DOIUrl":"10.1038/d41573-024-00117-0","url":null,"abstract":"","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":null,"pages":null},"PeriodicalIF":122.7,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141576945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Reactive oxygen species (ROS) in biological systems are transient but essential molecules that are generated and eliminated by a complex set of delicately balanced molecular machineries. Disruption of redox homeostasis has been associated with various human diseases, especially cancer, in which increased ROS levels are thought to have a major role in tumour development and progression. As such, modulation of cellular redox status by targeting ROS and their regulatory machineries is considered a promising therapeutic strategy for cancer treatment. Recently, there has been major progress in this field, including the discovery of novel redox signalling pathways that affect the metabolism of tumour cells as well as immune cells in the tumour microenvironment, and the intriguing ROS regulation of biomolecular phase separation. Progress has also been made in exploring redox regulation in cancer stem cells, the role of ROS in determining cell fate and new anticancer agents that target ROS. This Review discusses these research developments and their implications for cancer therapy and drug discovery, as well as emerging concepts, paradoxes and future perspectives. Reactive oxygen species are essential molecules that are generated and eliminated through complex balanced mechanisms. Increased reactive oxygen species levels have a role in tumour development, and targeting reactive oxygen species and their regulatory machineries is a promising therapeutic strategy. This Review discusses recent research developments in the field, their implications for cancer drug discovery, as well as emerging concepts and future perspectives.
{"title":"Targeting ROS in cancer: rationale and strategies","authors":"Christophe Glorieux, Shihua Liu, Dunyaporn Trachootham, Peng Huang","doi":"10.1038/s41573-024-00979-4","DOIUrl":"10.1038/s41573-024-00979-4","url":null,"abstract":"Reactive oxygen species (ROS) in biological systems are transient but essential molecules that are generated and eliminated by a complex set of delicately balanced molecular machineries. Disruption of redox homeostasis has been associated with various human diseases, especially cancer, in which increased ROS levels are thought to have a major role in tumour development and progression. As such, modulation of cellular redox status by targeting ROS and their regulatory machineries is considered a promising therapeutic strategy for cancer treatment. Recently, there has been major progress in this field, including the discovery of novel redox signalling pathways that affect the metabolism of tumour cells as well as immune cells in the tumour microenvironment, and the intriguing ROS regulation of biomolecular phase separation. Progress has also been made in exploring redox regulation in cancer stem cells, the role of ROS in determining cell fate and new anticancer agents that target ROS. This Review discusses these research developments and their implications for cancer therapy and drug discovery, as well as emerging concepts, paradoxes and future perspectives. Reactive oxygen species are essential molecules that are generated and eliminated through complex balanced mechanisms. Increased reactive oxygen species levels have a role in tumour development, and targeting reactive oxygen species and their regulatory machineries is a promising therapeutic strategy. This Review discusses recent research developments in the field, their implications for cancer drug discovery, as well as emerging concepts and future perspectives.","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":null,"pages":null},"PeriodicalIF":122.7,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-05DOI: 10.1038/d41573-024-00116-1
Asher Mullard
{"title":"FDA approves third anti-amyloid antibody for Alzheimer disease","authors":"Asher Mullard","doi":"10.1038/d41573-024-00116-1","DOIUrl":"10.1038/d41573-024-00116-1","url":null,"abstract":"","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":null,"pages":null},"PeriodicalIF":122.7,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141538284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：