Pub Date : 2024-10-18DOI: 10.1016/j.drudis.2024.104210
Lisa Bailey (Managing Director Insights and Head of DEI Strategy, Trinity Life Sciences)
{"title":"The Challenges and Opportunities in Clinical Trial Diversity","authors":"Lisa Bailey (Managing Director Insights and Head of DEI Strategy, Trinity Life Sciences)","doi":"10.1016/j.drudis.2024.104210","DOIUrl":"10.1016/j.drudis.2024.104210","url":null,"abstract":"","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 12","pages":"Article 104210"},"PeriodicalIF":6.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454528","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}
Pub Date : 2024-10-18DOI: 10.1016/j.drudis.2024.104213
Jim F. Zinken , Anna M.G. Pasmooij , Antwan G.H. Ederveen , Jarno Hoekman , Lourens T. Bloem
An environmental risk assessment (ERA) is mandatory for all applications for marketing authorisation of medicines in the European Union (EU). We investigated stakeholder perspectives on the role of the ERA in EU regulation of medicines for human use. We discuss the current position of the ERA and the current conduct and assessment of the ERA, such as the required expertise, data, and studies, its applicability to generic drugs, and its use in regulatory decision-making. We also discuss future perspectives, including extension of the ERA to cover antimicrobial resistance, improved risk mitigation, impact on ‘over-the-counter’ (OTC) status, and incorporation into reimbursement considerations.
在欧盟（EU），所有药品的上市许可申请都必须进行环境风险评估（ERA）。我们调查了利益相关者对环境风险评估在欧盟人用药品监管中的作用的看法。我们讨论了 ERA 的现状，包括 ERA 的开展和评估，如所需的专业知识、数据和研究，其对仿制药的适用性，以及在监管决策中的应用。我们还讨论了未来前景，包括将 ERA 扩展到抗菌药耐药性、改进风险缓解、对 "非处方药"（OTC）地位的影响以及纳入报销考虑因素。
{"title":"Environmental risk assessment in the EU regulation of medicines for human use: an analysis of stakeholder perspectives on its current and future role","authors":"Jim F. Zinken , Anna M.G. Pasmooij , Antwan G.H. Ederveen , Jarno Hoekman , Lourens T. Bloem","doi":"10.1016/j.drudis.2024.104213","DOIUrl":"10.1016/j.drudis.2024.104213","url":null,"abstract":"<div><div>An environmental risk assessment (ERA) is mandatory for all applications for marketing authorisation of medicines in the European Union (EU). We investigated stakeholder perspectives on the role of the ERA in EU regulation of medicines for human use. We discuss the current position of the ERA and the current conduct and assessment of the ERA, such as the required expertise, data, and studies, its applicability to generic drugs, and its use in regulatory decision-making. We also discuss future perspectives, including extension of the ERA to cover antimicrobial resistance, improved risk mitigation, impact on ‘over-the-counter’ (OTC) status, and incorporation into reimbursement considerations.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 12","pages":"Article 104213"},"PeriodicalIF":6.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-18DOI: 10.1016/j.drudis.2024.104216
Bilal Nehmeh , Joseph Rebehmed , Riham Nehmeh , Robin Taleb , Elias Akoury
Neurodegenerative diseases (NDs) pose serious healthcare challenges with limited therapeutic treatments and high social burdens. The integration of artificial intelligence (AI) into drug discovery has emerged as a promising approach to address these challenges. This review explores the application of AI techniques to unravel therapeutic frontiers for NDs. We examine the current landscape of AI-driven drug discovery and discuss the potentials of AI in accelerating the identification of novel therapeutic targets on ND research and drug development, optimization of drug candidates, and expediating personalized medicine approaches. Finally, we outline future directions and challenges in harnessing AI for the advancement of therapeutics in this critical area by emphasizing the importance of interdisciplinary collaboration and ethical considerations.
{"title":"Unlocking therapeutic frontiers: harnessing artificial intelligence in drug discovery for neurodegenerative diseases","authors":"Bilal Nehmeh , Joseph Rebehmed , Riham Nehmeh , Robin Taleb , Elias Akoury","doi":"10.1016/j.drudis.2024.104216","DOIUrl":"10.1016/j.drudis.2024.104216","url":null,"abstract":"<div><div>Neurodegenerative diseases (NDs) pose serious healthcare challenges with limited therapeutic treatments and high social burdens. The integration of artificial intelligence (AI) into drug discovery has emerged as a promising approach to address these challenges. This review explores the application of AI techniques to unravel therapeutic frontiers for NDs. We examine the current landscape of AI-driven drug discovery and discuss the potentials of AI in accelerating the identification of novel therapeutic targets on ND research and drug development, optimization of drug candidates, and expediating personalized medicine approaches. Finally, we outline future directions and challenges in harnessing AI for the advancement of therapeutics in this critical area by emphasizing the importance of interdisciplinary collaboration and ethical considerations.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 12","pages":"Article 104216"},"PeriodicalIF":6.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454530","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}
Genetic disorders (GDs) are challenging to treat owing to a lack of optimal treatment regimens and intricate and often difficult-to-understand underlying biological processes. Limited therapeutic approaches, which mostly provide symptomatic relief, are available. To date, a limited number of peptide-based drugs for the treatment of GDs are available, and several candidates are under clinical study. This review provides mechanistic insights into GDs and potential target areas where peptide-based drugs are beneficial. In addition, it emphasizes the usefulness of peptides as carriers for gene delivery, biomarkers for mutation detection and peptide-based vaccines for treating GDs.
{"title":"Peptide-based therapeutics targeting genetic disorders","authors":"Shweta Subramanian, Meenakshi Jain, Rajkumar Misra, Rahul Jain","doi":"10.1016/j.drudis.2024.104209","DOIUrl":"10.1016/j.drudis.2024.104209","url":null,"abstract":"<div><div>Genetic disorders (GDs) are challenging to treat owing to a lack of optimal treatment regimens and intricate and often difficult-to-understand underlying biological processes. Limited therapeutic approaches, which mostly provide symptomatic relief, are available. To date, a limited number of peptide-based drugs for the treatment of GDs are available, and several candidates are under clinical study. This review provides mechanistic insights into GDs and potential target areas where peptide-based drugs are beneficial. In addition, it emphasizes the usefulness of peptides as carriers for gene delivery, biomarkers for mutation detection and peptide-based vaccines for treating GDs.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 12","pages":"Article 104209"},"PeriodicalIF":6.5,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454526","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}
Pub Date : 2024-10-11DOI: 10.1016/j.drudis.2024.104208
Mohammad Imran , Peter Michael Moyle , Danielle Kamato , Yousuf Mohammed
The skin has an important role in regulating homeostasis and protecting the body from endogenous and exogenous microenvironments. Although 3D models for drug discovery have been extensively studied, there is a growing demand for more advanced 3D skin models to enhance skin research. The use of these advanced skin models holds promise across domains such as cosmetics, skin disease treatments, and toxicity testing of new therapeutics. Recent advances include the development of skin-on-a-chip, spheroids, reconstructed skin, organoids, and computational approaches, including quantitative structure–activity relationship (QSAR) and quantitative structure–property relationship (QSPR) research. These innovations are bridging the gap between traditional 2D and advanced 3D models, moving progress from research to clinical applications. In this review, we highlight in vitro and computational skin models with advanced drug discovery for skin-related applications.
{"title":"Advances in, and prospects of, 3D preclinical models for skin drug discovery","authors":"Mohammad Imran , Peter Michael Moyle , Danielle Kamato , Yousuf Mohammed","doi":"10.1016/j.drudis.2024.104208","DOIUrl":"10.1016/j.drudis.2024.104208","url":null,"abstract":"<div><div>The skin has an important role in regulating homeostasis and protecting the body from endogenous and exogenous microenvironments. Although 3D models for drug discovery have been extensively studied, there is a growing demand for more advanced 3D skin models to enhance skin research. The use of these advanced skin models holds promise across domains such as cosmetics, skin disease treatments, and toxicity testing of new therapeutics. Recent advances include the development of skin-on-a-chip, spheroids, reconstructed skin, organoids, and computational approaches, including quantitative structure–activity relationship (QSAR) and quantitative structure–property relationship (QSPR) research. These innovations are bridging the gap between traditional 2D and advanced 3D models, moving progress from research to clinical applications. In this review, we highlight <em>in vitro</em> and computational skin models with advanced drug discovery for skin-related applications.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 12","pages":"Article 104208"},"PeriodicalIF":6.5,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-11DOI: 10.1016/j.drudis.2024.104207
Simon Cruwys, Peter Hein, Bob Humphries, Darcey Black
Idiopathic pulmonary fibrosis (IPF) is an area of high unmet clinical need and high research activity in the pharmaceutical and biotech industries. The two approved therapies, nintedanib and pirfenidone, have issues with efficacy and tolerability. Despite a considerable number of development programs reaching late-stage Phase 2b or 3 clinical trials, no drug other than nintedanib and pirfenidone has successfully demonstrated a benefit for patients. An analysis of these failures, and consideration of the trajectories of some of the current development projects, may offer novel paradigms for choosing modes-of-action and for the development of successful drugs.
{"title":"Drug discovery and development in idiopathic pulmonary fibrosis: the changing landscape","authors":"Simon Cruwys, Peter Hein, Bob Humphries, Darcey Black","doi":"10.1016/j.drudis.2024.104207","DOIUrl":"10.1016/j.drudis.2024.104207","url":null,"abstract":"<div><div>Idiopathic pulmonary fibrosis (IPF) is an area of high unmet clinical need and high research activity in the pharmaceutical and biotech industries. The two approved therapies, nintedanib and pirfenidone, have issues with efficacy and tolerability. Despite a considerable number of development programs reaching late-stage Phase 2b or 3 clinical trials, no drug other than nintedanib and pirfenidone has successfully demonstrated a benefit for patients. An analysis of these failures, and consideration of the trajectories of some of the current development projects, may offer novel paradigms for choosing modes-of-action and for the development of successful drugs.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 11","pages":"Article 104207"},"PeriodicalIF":6.5,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454523","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}
Pub Date : 2024-10-10DOI: 10.1016/j.drudis.2024.104206
Henry O. Lamb , Aurélie H. Benfield , Sónia Troeira Henriques
Drug resistance is the leading cause of treatment failure in patients with cancer. Thus, innovative therapeutic strategies are required to overcome this critical challenge and improve patient outcomes. In this review, we examine the potential of peptide-based therapies to combat drug resistance in cancer. We highlight the unique strategies and mechanisms that can be explored by using peptides, including their ability to selectively target tumours, facilitate drug delivery into cancer cells, and inhibit key intracellular proteins that drive cancer progression and resistance. Peptides offer a promising approach to overcoming both intrinsic and adaptative cancer resistance against chemotherapy, targeted therapies, and biologics.
{"title":"Peptides as innovative strategies to combat drug resistance in cancer therapy","authors":"Henry O. Lamb , Aurélie H. Benfield , Sónia Troeira Henriques","doi":"10.1016/j.drudis.2024.104206","DOIUrl":"10.1016/j.drudis.2024.104206","url":null,"abstract":"<div><div>Drug resistance is the leading cause of treatment failure in patients with cancer. Thus, innovative therapeutic strategies are required to overcome this critical challenge and improve patient outcomes. In this review, we examine the potential of peptide-based therapies to combat drug resistance in cancer. We highlight the unique strategies and mechanisms that can be explored by using peptides, including their ability to selectively target tumours, facilitate drug delivery into cancer cells, and inhibit key intracellular proteins that drive cancer progression and resistance. Peptides offer a promising approach to overcoming both intrinsic and adaptative cancer resistance against chemotherapy, targeted therapies, and biologics.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 12","pages":"Article 104206"},"PeriodicalIF":6.5,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-09DOI: 10.1016/j.drudis.2024.104201
Elena F. Evans , Zeenat A. Shyr , Bryan J. Traynor , Wei Zheng
Rare diseases affect one in ten people but only a small fraction of these diseases have an FDA-approved treatment. Haploinsufficiency, caused by a dominant loss-of-function mutation, is a unique rare disease group because patients have one normal allele of the affected gene. This makes rare haploinsufficiency diseases promising candidates for drug development by increasing expression of the normal gene allele, decreasing the target protein degradation and enhancing the target protein function. This review summarizes recent progresses and approaches used in the translational research of therapeutics to treat haploinsufficiency diseases including gene therapy, nucleotide-based therapeutics and small-molecule drug development. We hope that these drug development strategies will accelerate therapeutic development to treat haploinsufficiency diseases.
{"title":"Therapeutic development approaches to treat haploinsufficiency diseases: restoring protein levels","authors":"Elena F. Evans , Zeenat A. Shyr , Bryan J. Traynor , Wei Zheng","doi":"10.1016/j.drudis.2024.104201","DOIUrl":"10.1016/j.drudis.2024.104201","url":null,"abstract":"<div><div>Rare diseases affect one in ten people but only a small fraction of these diseases have an FDA-approved treatment. Haploinsufficiency, caused by a dominant loss-of-function mutation, is a unique rare disease group because patients have one normal allele of the affected gene. This makes rare haploinsufficiency diseases promising candidates for drug development by increasing expression of the normal gene allele, decreasing the target protein degradation and enhancing the target protein function. This review summarizes recent progresses and approaches used in the translational research of therapeutics to treat haploinsufficiency diseases including gene therapy, nucleotide-based therapeutics and small-molecule drug development. We hope that these drug development strategies will accelerate therapeutic development to treat haploinsufficiency diseases.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 12","pages":"Article 104201"},"PeriodicalIF":6.5,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-09DOI: 10.1016/j.drudis.2024.104202
Vladimir M. Subbotin , Michael V. Subotin
While allograft loss due to acute rejection has been dramatically reduced due to the introduction of immunophilins, this therapy has little effect on allografts lost due to chronic vascular rejection. This situation may be due to a misnomer of the pathology. Specifically, its designation as ‘chronic rejection’ has given the wrong impression that the cause of the disease has been identified. Analyzing this phenomenon under the rubric of linguistic relativity suggests that the words chosen to name the disease may have restricted our cognitive ability to solve the problem. Thus, we have to step out of the ‘alloimmunity/rejection box’.
{"title":"The rejection that defies antirejection drugs—chronic vascular rejection (allograft vasculopathy): The role of terminology and linguistic relativity","authors":"Vladimir M. Subbotin , Michael V. Subotin","doi":"10.1016/j.drudis.2024.104202","DOIUrl":"10.1016/j.drudis.2024.104202","url":null,"abstract":"<div><div>While allograft loss due to acute rejection has been dramatically reduced due to the introduction of immunophilins, this therapy has little effect on allografts lost due to chronic vascular rejection. This situation may be due to a misnomer of the pathology. Specifically, its designation as ‘chronic rejection’ has given the wrong impression that the cause of the disease has been identified. Analyzing this phenomenon under the rubric of linguistic relativity suggests that the words chosen to name the disease may have restricted our cognitive ability to solve the problem. Thus, we have to step out of the ‘alloimmunity/rejection box’.</div><div> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!-->Let’s pause between our words,</div><div> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!-->Speak and fall silent again,</div><div> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!-->So that the meaning of the word just spoken,</div><div> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!-->Sounds a clearer echo in our heads.</div><div> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!-->Let’s pause between our words.</div><div> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!-->Andrey Makarevich.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 12","pages":"Article 104202"},"PeriodicalIF":6.5,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142398899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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