Pub Date : 2023-07-01DOI: 10.1177/02611929231180455
{"title":"2022 Michael Balls Award.","authors":"","doi":"10.1177/02611929231180455","DOIUrl":"https://doi.org/10.1177/02611929231180455","url":null,"abstract":"","PeriodicalId":55577,"journal":{"name":"Atla-Alternatives To Laboratory Animals","volume":"51 4","pages":"222-223"},"PeriodicalIF":2.7,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9855769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-01DOI: 10.1177/02611929231180428
Nikita Narayan Naik, Bharadwaja Vadloori, Suresh Poosala, Pratima Srivastava, Sandra Coecke, Adrian Smith, Aysha Akhtar, Clive Roper, Sridhar Radhakrishnan, Balaji Bhyravbhatla, Madhujit Damle, Venkat Koushik Pulla, Johannes Hackethal, Reyk Horland, Albert P Li, Falguni Pati, Manu Smriti Singh, Paola Occhetta, Rohit Bisht, Prajakta Dandekar, Krishna Bhagavatula, Dasja Pajkrt, Michael Johnson, Tilo Weber, John Huang, Lisiena Hysenaj, Banerjee Mallar, Bhat Ramray, Santosh Dixit, Shreekanth Joshi, Mandar Kulkarni
Animal experimentation has been integral to drug discovery and development and safety assessment for many years, since it provides insights into the mechanisms of drug efficacy and toxicity (e.g. pharmacology, pharmacokinetics and pharmacodynamics). However, due to species differences in physiology, metabolism and sensitivity to drugs, the animal models can often fail to replicate the effects of drugs and chemicals in human patients, workers and consumers. Researchers across the globe are increasingly applying the Three Rs principles by employing innovative methods in research and testing. The Three Rs concept focuses on: the replacement of animal models (e.g. with in vitro and in silico models or human studies), on the reduction of the number of animals required to achieve research objectives, and on the refinement of existing experimental practices (e.g. eliminating distress and enhancing animal wellbeing). For the last two years, Oncoseek Bio-Acasta Health, a 3-D cell culture-based cutting-edge translational biotechnology company, has organised an annual International Conference on 3Rs Research and Progress. This series of global conferences aims to bring together researchers with diverse expertise and interests, and provides a platform where they can share and discuss their research to promote practices according to the Three Rs principles. In November 2022, the 3rd international conference, Advances in Animal Models and Cutting-Edge Research in Alternatives, took place at the GITAM University in Vishakhapatnam (AP, India) in a hybrid format (i.e. online and in-person). These conference proceedings provide details of the presentations, which were categorised under five different topic sessions. It also describes a special interactive session on in silico strategies for preclinical research in oncology, which was held at the end of the first day.
{"title":"Advances in Animal Models and Cutting-Edge Research in Alternatives: Proceedings of the Third International Conference on 3Rs Research and Progress, Vishakhapatnam, 2022.","authors":"Nikita Narayan Naik, Bharadwaja Vadloori, Suresh Poosala, Pratima Srivastava, Sandra Coecke, Adrian Smith, Aysha Akhtar, Clive Roper, Sridhar Radhakrishnan, Balaji Bhyravbhatla, Madhujit Damle, Venkat Koushik Pulla, Johannes Hackethal, Reyk Horland, Albert P Li, Falguni Pati, Manu Smriti Singh, Paola Occhetta, Rohit Bisht, Prajakta Dandekar, Krishna Bhagavatula, Dasja Pajkrt, Michael Johnson, Tilo Weber, John Huang, Lisiena Hysenaj, Banerjee Mallar, Bhat Ramray, Santosh Dixit, Shreekanth Joshi, Mandar Kulkarni","doi":"10.1177/02611929231180428","DOIUrl":"https://doi.org/10.1177/02611929231180428","url":null,"abstract":"<p><p>Animal experimentation has been integral to drug discovery and development and safety assessment for many years, since it provides insights into the mechanisms of drug efficacy and toxicity (e.g. pharmacology, pharmacokinetics and pharmacodynamics). However, due to species differences in physiology, metabolism and sensitivity to drugs, the animal models can often fail to replicate the effects of drugs and chemicals in human patients, workers and consumers. Researchers across the globe are increasingly applying the Three Rs principles by employing innovative methods in research and testing. The Three Rs concept focuses on: the <i>replacement</i> of animal models (e.g. with <i>in vitro</i> and <i>in silico</i> models or human studies), on the <i>reduction</i> of the number of animals required to achieve research objectives, and on the <i>refinement</i> of existing experimental practices (e.g. eliminating distress and enhancing animal wellbeing). For the last two years, Oncoseek Bio-Acasta Health, a 3-D cell culture-based cutting-edge translational biotechnology company, has organised an annual International Conference on 3Rs Research and Progress. This series of global conferences aims to bring together researchers with diverse expertise and interests, and provides a platform where they can share and discuss their research to promote practices according to the Three Rs principles. In November 2022, the 3rd international conference, <i>Advances in Animal Models and Cutting-Edge Research in Alternatives</i>, took place at the GITAM University in Vishakhapatnam (AP, India) in a hybrid format (i.e. online and in-person). These conference proceedings provide details of the presentations, which were categorised under five different topic sessions. It also describes a special interactive session on <i>in silico</i> strategies for preclinical research in oncology, which was held at the end of the first day.</p>","PeriodicalId":55577,"journal":{"name":"Atla-Alternatives To Laboratory Animals","volume":"51 4","pages":"263-288"},"PeriodicalIF":2.7,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10231991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The significance of angiogenesis in tumour progression has been widely documented. Hence, the identification of anti-angiogenic agents with fewer common side effects would be valuable in cancer therapy. In this study, we evaluated the anti-angiogenic and anti-proliferative effects of a hydro-alcoholic extract of fenugreek seed (HAEF) on human umbilical vein endothelial cells (HUVECs). Human umbilical vein endothelial cells were treated with various concentrations of HAEF and the half-maximal inhibitory concentration (IC50) value was estimated by using the MTT assay. Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and matrix metalloproteinase enzyme (MMP-2 and MMP-9) gene expression profiles were evaluated by using quantitative RT-PCR (qRT-PCR). Moreover, MMP activities and PI3K, Akt and cyclin D1 protein expression levels were evaluated by gel zymography and Western blotting, respectively. HAEF reduced HUVEC viability, with an IC50 value of 200 μg/ml. The qRT-PCR results demonstrated that treatment with HAEF markedly reduced MMP-2/MMP-9, VEGF and bFGF gene expression, as compared to the control group. We also found that MMP-2/MMP-9 enzyme activity and PI3K/Akt/cyclin D1 protein expression were notably decreased in cells treated with HAEF. Our results suggest that HAEF can potentially inhibit angiogenesis, and also affect cellular proliferation by targeting the PI3K/Akt/cyclin D1 pathway. Thus, fenugreek seed extract merits further investigation as a source of compounds with anti-cancer properties.
{"title":"Fenugreek Seed Extract Regulates Human Umbilical Vein Endothelial Cell Angiogenesis and Proliferation via the PI3K/Akt/Cyclin D1 Pathway.","authors":"Samaneh Safarpour, Farshad Mirzavi, Farzad Rahmani, Fatemeh Forouzanfar, Hamid Reza Sadeghnia, Baratali Mashkani, Daryoush Hamidi Alamdari, Mohammad Soukhtanloo","doi":"10.1177/02611929231181623","DOIUrl":"10.1177/02611929231181623","url":null,"abstract":"<p><p>The significance of angiogenesis in tumour progression has been widely documented. Hence, the identification of anti-angiogenic agents with fewer common side effects would be valuable in cancer therapy. In this study, we evaluated the anti-angiogenic and anti-proliferative effects of a hydro-alcoholic extract of fenugreek seed (HAEF) on human umbilical vein endothelial cells (HUVECs). Human umbilical vein endothelial cells were treated with various concentrations of HAEF and the half-maximal inhibitory concentration (IC<sub>50</sub>) value was estimated by using the MTT assay. Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and matrix metalloproteinase enzyme (MMP-2 and MMP-9) gene expression profiles were evaluated by using quantitative RT-PCR (qRT-PCR). Moreover, MMP activities and PI3K, Akt and cyclin D1 protein expression levels were evaluated by gel zymography and Western blotting, respectively. HAEF reduced HUVEC viability, with an IC<sub>50</sub> value of 200 μg/ml. The qRT-PCR results demonstrated that treatment with HAEF markedly reduced MMP-2/MMP-9, VEGF and bFGF gene expression, as compared to the control group. We also found that MMP-2/MMP-9 enzyme activity and PI3K/Akt/cyclin D1 protein expression were notably decreased in cells treated with HAEF. Our results suggest that HAEF can potentially inhibit angiogenesis, and also affect cellular proliferation by targeting the PI3K/Akt/cyclin D1 pathway. Thus, fenugreek seed extract merits further investigation as a source of compounds with anti-cancer properties.</p>","PeriodicalId":55577,"journal":{"name":"Atla-Alternatives To Laboratory Animals","volume":"51 4","pages":"249-257"},"PeriodicalIF":2.7,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10206735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-01DOI: 10.1177/02611929231180502
The FRAME Innovation Grant funding stream provides small grants for studies that will support the replacement of animals in biomedical research. FRAME launched the annual Innovation Grant scheme in 2021 to address a gap in the availability of small funding pots for proof-of-principle research and pilot projects. The scheme offers grants of around £5000, but will consider applications asking for up to £15,000. Projects should last between six months and two years. The first two years of this scheme proved to be very popular and resulted in the funding of some diverse and interesting projects. The grants represent a pilot project funding stream, to enable scientists to explore innovative ideas, methods and techniques and, where relevant, to generate proof-ofprinciple data to support applications for larger grants in the future. All applications for funding will be assessed by a panel of academics, FRAME staff and, where possible, an expert in the relevant field, according to the following key criteria:
{"title":"Spotlight on Three Rs Progress.","authors":"","doi":"10.1177/02611929231180502","DOIUrl":"https://doi.org/10.1177/02611929231180502","url":null,"abstract":"The FRAME Innovation Grant funding stream provides small grants for studies that will support the replacement of animals in biomedical research. FRAME launched the annual Innovation Grant scheme in 2021 to address a gap in the availability of small funding pots for proof-of-principle research and pilot projects. The scheme offers grants of around £5000, but will consider applications asking for up to £15,000. Projects should last between six months and two years. The first two years of this scheme proved to be very popular and resulted in the funding of some diverse and interesting projects. The grants represent a pilot project funding stream, to enable scientists to explore innovative ideas, methods and techniques and, where relevant, to generate proof-ofprinciple data to support applications for larger grants in the future. All applications for funding will be assessed by a panel of academics, FRAME staff and, where possible, an expert in the relevant field, according to the following key criteria:","PeriodicalId":55577,"journal":{"name":"Atla-Alternatives To Laboratory Animals","volume":"51 4","pages":"217-219"},"PeriodicalIF":2.7,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10231972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-01DOI: 10.1177/02611929231175315
Changes to cosmetics regulations internationally have been instrumental in the move away from animal testing and toward the development and promotion of alternative methods. Brazil is one of the largest markets for personal care and cosmetics products in the world and on 1st March 2023, as Resolution No. 58/2023 came into force, Brazil joined over 40 countries moving towards a global ban on the testing of cosmetic ingredients on animals. It is encouraging to witness not only the ongoing progress in governmental policies in mandating alternatives to animals, but also the continual innovations in the associated science. Whilst, currently, there is significant focus on applications in cosmetics, success in this arena will undoubtedly drive forward the use and acceptance of alternatives in other areas. Further details on the Brazilian Resolution are given in the Spotlight on Three Rs Progress section of this issue. This section also includes summaries of different studies that are applying a diverse range of alternative methods, from bioprinting of reconstructed human epidermis for assessing skin irritation, to open-source software that can quantify animal behaviours. Studies on the effects of SARSCoV-2 on the developing fetal brain and a model for human ovarian follicles are also highlighted. The review article by da Silva and Valadares also focuses attention on SARS-CoV-2 and how the pandemic highlighted the need for improvements in non-animal based methods in preclinical research for respiratory diseases. Here, the authors provide a detailed review of key methods that can be applied in this area, including: monolayer cell cultures; air–liquid interface models; lung organoids; human precision-cut lung slices (PCLS); and lung-on-a-chip microfluidic systems. The advantages and limitations of each method are discussed, as well as the need for standardisation and quality control procedures to make these New Approach Methodologies (NAMs) more acceptable for regulatory purposes. The importance of selecting the most appropriate models and endpoints to measure, depending on the research question, is emphasised. Andersson et al. also propose an addition to what they describe as the “NAM-based predictive toolbox”. These authors report an in silicomethod that can be used to differentiate liquids with the potential for eliciting eye irritation, from those considered to be non-irritant. The authors describe a two-tier approach that identifies potential irritants by using predicted pKa values and also by using a model that is derived from Hansen Solubility Parameters. The model performed well, and in order to err on the side of caution, it has been optimised to give a low rate of false negative predictions. The last two articles in this issue both present results from assays for toxicity testing. Hautenen et al. present the results of a study to develop an assay to assess the induction of vasculature formation — a mechanism associated with non-genotoxic carcinog
{"title":"Editorial.","authors":"","doi":"10.1177/02611929231175315","DOIUrl":"https://doi.org/10.1177/02611929231175315","url":null,"abstract":"Changes to cosmetics regulations internationally have been instrumental in the move away from animal testing and toward the development and promotion of alternative methods. Brazil is one of the largest markets for personal care and cosmetics products in the world and on 1st March 2023, as Resolution No. 58/2023 came into force, Brazil joined over 40 countries moving towards a global ban on the testing of cosmetic ingredients on animals. It is encouraging to witness not only the ongoing progress in governmental policies in mandating alternatives to animals, but also the continual innovations in the associated science. Whilst, currently, there is significant focus on applications in cosmetics, success in this arena will undoubtedly drive forward the use and acceptance of alternatives in other areas. Further details on the Brazilian Resolution are given in the Spotlight on Three Rs Progress section of this issue. This section also includes summaries of different studies that are applying a diverse range of alternative methods, from bioprinting of reconstructed human epidermis for assessing skin irritation, to open-source software that can quantify animal behaviours. Studies on the effects of SARSCoV-2 on the developing fetal brain and a model for human ovarian follicles are also highlighted. The review article by da Silva and Valadares also focuses attention on SARS-CoV-2 and how the pandemic highlighted the need for improvements in non-animal based methods in preclinical research for respiratory diseases. Here, the authors provide a detailed review of key methods that can be applied in this area, including: monolayer cell cultures; air–liquid interface models; lung organoids; human precision-cut lung slices (PCLS); and lung-on-a-chip microfluidic systems. The advantages and limitations of each method are discussed, as well as the need for standardisation and quality control procedures to make these New Approach Methodologies (NAMs) more acceptable for regulatory purposes. The importance of selecting the most appropriate models and endpoints to measure, depending on the research question, is emphasised. Andersson et al. also propose an addition to what they describe as the “NAM-based predictive toolbox”. These authors report an in silicomethod that can be used to differentiate liquids with the potential for eliciting eye irritation, from those considered to be non-irritant. The authors describe a two-tier approach that identifies potential irritants by using predicted pKa values and also by using a model that is derived from Hansen Solubility Parameters. The model performed well, and in order to err on the side of caution, it has been optimised to give a low rate of false negative predictions. The last two articles in this issue both present results from assays for toxicity testing. Hautenen et al. present the results of a study to develop an assay to assess the induction of vasculature formation — a mechanism associated with non-genotoxic carcinog","PeriodicalId":55577,"journal":{"name":"Atla-Alternatives To Laboratory Animals","volume":"51 3","pages":"155-156"},"PeriodicalIF":2.7,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9570332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-01DOI: 10.1177/02611929231170668
The Brazilian National Council for the Control of Animal Experimentation (CONCEA) has prohibited the use of animals, except human beings, in research for the development of cosmetics, hygiene products and perfumes. CONCEA is linked to the Ministry of Science and Technology, and the decision was published in the Brazilian Official Gazette on 1 March 2023. The measure states that it is mandatory, in Brazil, to adopt alternative methods that reduce the use of animals in this type of studies, stating that: “The use of vertebrate animals, except human beings, in scientific research and in the development and quality control of personal hygiene products, cosmetics, and perfumes that use in their formulations ingredients or compounds with safety and efficacy already scientifically proven is prohibited.” This approval follows the publication of a series of normative resolutions by the council over the last years recognising the applications of alternative methods that could replace animal testing.
{"title":"Spotlight on Three Rs Progress.","authors":"","doi":"10.1177/02611929231170668","DOIUrl":"https://doi.org/10.1177/02611929231170668","url":null,"abstract":"The Brazilian National Council for the Control of Animal Experimentation (CONCEA) has prohibited the use of animals, except human beings, in research for the development of cosmetics, hygiene products and perfumes. CONCEA is linked to the Ministry of Science and Technology, and the decision was published in the Brazilian Official Gazette on 1 March 2023. The measure states that it is mandatory, in Brazil, to adopt alternative methods that reduce the use of animals in this type of studies, stating that: “The use of vertebrate animals, except human beings, in scientific research and in the development and quality control of personal hygiene products, cosmetics, and perfumes that use in their formulations ingredients or compounds with safety and efficacy already scientifically proven is prohibited.” This approval follows the publication of a series of normative resolutions by the council over the last years recognising the applications of alternative methods that could replace animal testing.","PeriodicalId":55577,"journal":{"name":"Atla-Alternatives To Laboratory Animals","volume":"51 3","pages":"157-158"},"PeriodicalIF":2.7,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9938328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-01DOI: 10.1177/02611929231175676
Martin Andersson, Ulf Norinder, Swapnil Chavan, Ian Cotgreave
An in silico method has been developed that permits the binary differentiation between pure liquids causing serious eye damage or eye irritation, and pure liquids with no need for such classification, according to the UN GHS system. The method is based on the finding that the Hansen Solubility Parameters (HSP) of a liquid are collectively important predictors for eye irritation. Thus, by applying a two-tier approach in which in silico-predicted pKa values (firstly) and a trained model based solely on in silico-predicted HSP data (secondly) were used, we have developed, and validated, a fully in silico approach for predicting the outcome of a Draize test (in terms of UN GHS Cat. 1/Cat. 2A/Cat. 2B or UN GHS No Cat.) with high validation set performance (sensitivity = 0.846, specificity = 0.818, balanced accuracy = 0.832) using SMILES only. The method is applicable to pure non-ionic liquids with molecular weight below 500 g/mol, fewer than six hydrogen bond donors (e.g. nitrogen-hydrogen or oxygen-hydrogen bonds) and fewer than eleven hydrogen bond acceptors (e.g. nitrogen or oxygen atoms). Due to its fully in silico characteristics, this method can be applied to pure liquids that are still at the desktop design stage and not yet in production.
{"title":"<i>In Silico</i> Prediction of Eye Irritation Using Hansen Solubility Parameters and Predicted pKa Values.","authors":"Martin Andersson, Ulf Norinder, Swapnil Chavan, Ian Cotgreave","doi":"10.1177/02611929231175676","DOIUrl":"https://doi.org/10.1177/02611929231175676","url":null,"abstract":"<p><p>An <i>in silico</i> method has been developed that permits the binary differentiation between pure liquids causing serious eye damage or eye irritation, and pure liquids with no need for such classification, according to the UN GHS system. The method is based on the finding that the Hansen Solubility Parameters (HSP) of a liquid are collectively important predictors for eye irritation. Thus, by applying a two-tier approach in which <i>in silico</i>-predicted pKa values (firstly) and a trained model based solely on <i>in silico</i>-predicted HSP data (secondly) were used, we have developed, and validated, a fully <i>in silico</i> approach for predicting the outcome of a Draize test (in terms of UN GHS Cat. 1/Cat. 2A/Cat. 2B or UN GHS No Cat.) with high validation set performance (sensitivity = 0.846, specificity = 0.818, balanced accuracy = 0.832) using SMILES only. The method is applicable to pure non-ionic liquids with molecular weight below 500 g/mol, fewer than six hydrogen bond donors (e.g. nitrogen-hydrogen or oxygen-hydrogen bonds) and fewer than eleven hydrogen bond acceptors (e.g. nitrogen or oxygen atoms). Due to its fully <i>in silico</i> characteristics, this method can be applied to pure liquids that are still at the desktop design stage and not yet in production.</p>","PeriodicalId":55577,"journal":{"name":"Atla-Alternatives To Laboratory Animals","volume":"51 3","pages":"204-209"},"PeriodicalIF":2.7,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9625352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-01DOI: 10.1177/02611929231170392
Artur C G da Silva, Marize C Valadares
The SARS-CoV-2 outbreak focused global attention on the shortcomings of the drug discovery process. It led to its acceleration in several areas, particularly in the processes associated with the development and approval of COVID-19 vaccines. This situation contrasts with the low approval rates of new drugs for respiratory system diseases (e.g. asthma, chronic obstructive pulmonary disease, cancer, tuberculosis), which are leading causes of morbidity and mortality worldwide. In this context, innovation in respiratory system drug discovery is surely needed, and it is most likely to succeed through the use of preclinical models that are cost-effective, high-throughput and generate predictive human-relevant outcomes. Here, we highlight several non-animal new approach methodologies (NAMs) and their applications in respiratory research. We describe their potential uses for efficacy and toxicity assessments, to optimise the drug development process and reduce the high failure rates in clinical trials.
{"title":"The Application of New Approach Methodologies in Respiratory Disease Research: Their Role in Improving Translational Medicine from Bench to Bedside.","authors":"Artur C G da Silva, Marize C Valadares","doi":"10.1177/02611929231170392","DOIUrl":"https://doi.org/10.1177/02611929231170392","url":null,"abstract":"<p><p>The SARS-CoV-2 outbreak focused global attention on the shortcomings of the drug discovery process. It led to its acceleration in several areas, particularly in the processes associated with the development and approval of COVID-19 vaccines. This situation contrasts with the low approval rates of new drugs for respiratory system diseases (e.g. asthma, chronic obstructive pulmonary disease, cancer, tuberculosis), which are leading causes of morbidity and mortality worldwide. In this context, innovation in respiratory system drug discovery is surely needed, and it is most likely to succeed through the use of preclinical models that are cost-effective, high-throughput and generate predictive human-relevant outcomes. Here, we highlight several non-animal new approach methodologies (NAMs) and their applications in respiratory research. We describe their potential uses for efficacy and toxicity assessments, to optimise the drug development process and reduce the high failure rates in clinical trials.</p>","PeriodicalId":55577,"journal":{"name":"Atla-Alternatives To Laboratory Animals","volume":"51 3","pages":"161-174"},"PeriodicalIF":2.7,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9926909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}