Biomarker Insights最新文献_第9页

Biomarkers: Opportunities and Challenges for Drug Development in the Current Regulatory Landscape. 生物标志物:当前监管环境下药物开发的机遇与挑战。

IF 3.8

Biomarker Insights Pub Date : 2020-12-08 eCollection Date: 2020-01-01 DOI: 10.1177/1177271920974652

Mariya Gromova, Annegret Vaggelas, Gabriele Dallmann, Diane Seimetz

{"title":"Biomarkers: Opportunities and Challenges for Drug Development in the Current Regulatory Landscape.","authors":"Mariya Gromova, Annegret Vaggelas, Gabriele Dallmann, Diane Seimetz","doi":"10.1177/1177271920974652","DOIUrl":"https://doi.org/10.1177/1177271920974652","url":null,"abstract":"Biomarkers are widely used at every stage of drug discovery and development. Utilisation of biomarkers has a potential to make drug discovery, development and approval processes more efficient. An overview of the current global regulatory landscape is presented in this article with particular emphasis on the validation and qualification of biomarkers, as well as legal framework for companion diagnostics. Furthermore, this article shows how the number of approved drugs with at least 1 biomarker used during development (biomarker acceptance) is affected by the recent advances in the biomarker regulations. More than half of analysed approvals were supported by biomarker data and there has been a slight increase in acceptance of biomarkers in recent years, even though the growth is not continuous. For certain pharmacotherapeutic groups, approvals with biomarkers are more common than without. Examples include immunosuppressants, immunostimulants, drugs used in diabetes, antithrombotic drugs, antineoplastic agents and antivirals. As a conclusion, potential benefits, challenges and opportunities of using biomarkers in drug discovery and development in the current regulatory landscape are summarised and discussed.","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2020-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1177271920974652","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38732988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 33

A Paradigm to Discover Biomarkers Associated With Chronic Kidney Disease Progression. 发现与慢性肾脏疾病进展相关的生物标志物的范例。

IF 3.8

Biomarker Insights Pub Date : 2020-12-01 eCollection Date: 2020-01-01 DOI: 10.1177/1177271920976146

Ibrahim Ali, Sara T Ibrahim, Rajkumar Chinnadurai, Darren Green, Maarten Taal, Tony D Whetton, Philip A Kalra

引用次数: 0

Biomarkers: Our Path Towards a Cure for Alzheimer Disease. 生物标志物:我们治疗阿尔茨海默病的途径。

IF 3.8

Biomarker Insights Pub Date : 2020-11-25 eCollection Date: 2020-01-01 DOI: 10.1177/1177271920976367

Rawan Tarawneh

{"title":"Biomarkers: Our Path Towards a Cure for Alzheimer Disease.","authors":"Rawan Tarawneh","doi":"10.1177/1177271920976367","DOIUrl":"https://doi.org/10.1177/1177271920976367","url":null,"abstract":"Over the last decade, biomarkers have significantly improved our understanding of the pathophysiology of Alzheimer disease (AD) and provided valuable tools to examine different disease mechanisms and their progression over time. While several markers of amyloid, tau, neuronal, synaptic, and axonal injury, inflammation, and immune dysregulation in AD have been identified, there is a relative paucity of biomarkers which reflect other disease mechanisms such as oxidative stress, mitochondrial injury, vascular or endothelial injury, and calcium-mediated excitotoxicity. Importantly, there is an urgent need to standardize methods for biomarker assessments across different centers, and to identify dynamic biomarkers which can monitor disease progression over time and/or response to potential disease-modifying treatments. The updated research framework for AD, proposed by the National Institute of Aging- Alzheimer's Association (NIA-AA) Work Group, emphasizes the importance of incorporating biomarkers in AD research and defines AD as a biological construct consisting of amyloid, tau, and neurodegeneration which spans pre-symptomatic and symptomatic stages. As results of clinical trials of AD therapeutics have been disappointing, it has become increasingly clear that the success of future AD trials will require the incorporation of biomarkers in participant selection, prognostication, monitoring disease progression, and assessing response to treatments. We here review the current state of fluid AD biomarkers, and discuss the advantages and limitations of the updated NIA-AA research framework. Importantly, the integration of biomarker data with clinical, cognitive, and imaging domains through a systems biology approach will be essential to adequately capture the molecular, genetic, and pathological heterogeneity of AD and its spatiotemporal evolution over time.","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2020-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1177271920976367","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38688446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 17

Biobanking for Cancer Biomarker Research: Issues and Solutions. 癌症生物标志物研究的生物银行:问题与解决方案。

IF 3.8

Biomarker Insights Pub Date : 2020-10-19 eCollection Date: 2020-01-01 DOI: 10.1177/1177271920965522

Lise A Matzke, Peter H Watson

引用次数: 12

Clusterin as a Potential Biomarker of Obesity-Related Alzheimer's Disease Risk. 簇蛋白作为肥胖相关阿尔茨海默病风险的潜在生物标志物

IF 3.8

Biomarker Insights Pub Date : 2020-10-12 eCollection Date: 2020-01-01 DOI: 10.1177/1177271920964108

David Bradley

{"title":"Clusterin as a Potential Biomarker of Obesity-Related Alzheimer's Disease Risk.","authors":"David Bradley","doi":"10.1177/1177271920964108","DOIUrl":"https://doi.org/10.1177/1177271920964108","url":null,"abstract":"Over 35% of the adult US population is obese. In turn, excess adiposity increases the risk of multiple complications including type 2 diabetes (T2D), insulin resistance, and cardiovascular disease; yet, obesity also independently heightens risk of Alzheimer's Disease (AD), even after adjusting for other important confounding risk factors including blood pressure, sociodemographics, cholesterol levels, smoking status, and Apolipoprotein E (ApoE) genotype. Among patients over the age of 65 with dementia, 37% have coexisting diabetes, and an estimated 7.3% of cases of AD are directly attributable to midlife obesity. Clusterin, also known as apolipoprotein J (ApoJ), is a multifunctional glycoprotein that acts as a molecular chaperone, assisting folding of secreted proteins. Clusterin has been implicated in several physiological and pathological states, including AD, metabolic disease, and cardiovascular disease. Despite long-standing interest in elucidating clusterin's relationship with amyloid beta (Aβ) aggregation/clearance and toxicity, significant knowledge gaps still exist. Altered clusterin expression and protein levels have been linked with cognitive and memory function, disrupted central nervous system lipid flux, as well as pathogenic brain structure; and its role in cardiometabolic disease suggests that it may be a link between insulin resistance, dyslipidemia, and AD. Here, we briefly highlight clusterin's relevance to AD by presenting existing evidence linking clusterin to AD and cardiometabolic disease, and discussing its potential utility as a biomarker for AD in the presence of obesity-related metabolic disease.","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2020-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1177271920964108","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38629754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 9

Unraveling Pathophysiological Mechanisms of Parkinson's Disease: Contribution of CSF Biomarkers. 揭示帕金森病的病理生理机制:脑脊液生物标志物的贡献。

IF 3.8

Biomarker Insights Pub Date : 2020-10-12 eCollection Date: 2020-01-01 DOI: 10.1177/1177271920964077

Lucia Farotti, Federico Paolini Paoletti, Simone Simoni, Lucilla Parnetti

{"title":"Unraveling Pathophysiological Mechanisms of Parkinson's Disease: Contribution of CSF Biomarkers.","authors":"Lucia Farotti, Federico Paolini Paoletti, Simone Simoni, Lucilla Parnetti","doi":"10.1177/1177271920964077","DOIUrl":"https://doi.org/10.1177/1177271920964077","url":null,"abstract":"Diagnosis of Parkinson's disease (PD) relies on clinical history and physical examination, but misdiagnosis is common in early stages. Identification of biomarkers for PD may allow for early and more precise diagnosis and provide information about prognosis. Developments in analytical chemistry allow for the detection of a large number of molecules in cerebrospinal fluid (CSF), which are known to be associated with the pathogenesis of PD. Given the pathophysiology of PD, CSF α-synuclein species have the strongest rationale for use, also providing encouraging preliminary results in terms of early diagnosis. In the field of classical Alzheimer's disease (AD) biomarkers, low CSF Aβ42 levels have shown a robust prognostic value in terms of development of cognitive impairment. Other CSF biomarkers including lysosomal enzymes, neurofilament light chain, markers of neuroinflammation and oxidative stress, although promising, have not proved to be reliable for diagnostic and prognostic purposes yet. Overall, the implementation of CSF biomarkers may give a substantial contribution to the optimal use of disease-modifying drugs.","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2020-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1177271920964077","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38629753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Single Center "Snapshot" Experience With Donor-Derived Cell-Free DNA After Lung Transplantation. 单中心 "快照 "经验：肺移植术后的捐献者无细胞 DNA

IF 3.8

Biomarker Insights Pub Date : 2020-09-16 eCollection Date: 2020-01-01 DOI: 10.1177/1177271920958704

Deborah Jo Levine, David J Ross, Edward Sako

引用次数: 0

Non-Targeted Metabolomic Analysis Reveals Serum Phospholipid Alterations in Patients with Early Stages of Diabetic Foot Ulcer. 非靶向代谢组学分析揭示早期糖尿病足溃疡患者血清磷脂改变

IF 3.8

Biomarker Insights Pub Date : 2020-09-09 eCollection Date: 2020-01-01 DOI: 10.1177/1177271920954828

Ignacio I Álvarez-Rodríguez, Eduardo Castaño-Tostado, David G García-Gutiérrez, Rosalía Reynoso-Camacho, Juana E Elton-Puente, Alicia Barajas-Pozos, Iza F Pérez-Ramírez

{"title":"Non-Targeted Metabolomic Analysis Reveals Serum Phospholipid Alterations in Patients with Early Stages of Diabetic Foot Ulcer.","authors":"Ignacio I Álvarez-Rodríguez, Eduardo Castaño-Tostado, David G García-Gutiérrez, Rosalía Reynoso-Camacho, Juana E Elton-Puente, Alicia Barajas-Pozos, Iza F Pérez-Ramírez","doi":"10.1177/1177271920954828","DOIUrl":"https://doi.org/10.1177/1177271920954828","url":null,"abstract":"Diabetic foot ulcer (DFU) is a common complication of type 2 diabetes mellitus (T2DM) characterized by ulcer formation, which can lead to the amputation of lower extremities. However, the metabolic alterations related to this complication are not completely elucidated. Therefore, we carried out a metabolomic analysis of serum samples obtained from T2DM adult patients diagnosed with diabetic foot ulcer in a cross-sectional, observational, and comparative study. Eighty-four volunteers were classified into the following groups: without T2DM (control group, n = 30) and with T2DM and different stages of diabetic foot ulcer according to Wagner-Meggitt classification system: DFU G0 (n = 11), DFU G1 (n = 14), DFU G2 (n = 16), and DFU G3 (n = 13). The non-target metabolomic profile followed by chemometric analysis revealed that lysophosphatidylethanolamine (16:1) could be proposed as key metabolite related to the onset of diabetic foot ulcer; however, this phospholipid was not affected by diabetic foot ulcer progression. Therefore, further studies are necessary to validate these phospholipids as biomarker candidates for the early diagnosis of diabetic foot ulcer in T2DM patients.","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2020-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1177271920954828","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38496160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Fluid Biomarkers for Synaptic Dysfunction and Loss. 突触功能障碍和丧失的液体生物标志物。

IF 3.8

Biomarker Insights Pub Date : 2020-08-21 eCollection Date: 2020-01-01 DOI: 10.1177/1177271920950319

Elena Camporesi, Johanna Nilsson, Ann Brinkmalm, Bruno Becker, Nicholas J Ashton, Kaj Blennow, Henrik Zetterberg

{"title":"Fluid Biomarkers for Synaptic Dysfunction and Loss.","authors":"Elena Camporesi, Johanna Nilsson, Ann Brinkmalm, Bruno Becker, Nicholas J Ashton, Kaj Blennow, Henrik Zetterberg","doi":"10.1177/1177271920950319","DOIUrl":"10.1177/1177271920950319","url":null,"abstract":"Synapses are the site for brain communication where information is transmitted between neurons and stored for memory formation. Synaptic degeneration is a global and early pathogenic event in neurodegenerative disorders with reduced levels of pre- and postsynaptic proteins being recognized as a core feature of Alzheimer’s disease (AD) pathophysiology. Together with AD, other neurodegenerative and neurodevelopmental disorders show altered synaptic homeostasis as an important pathogenic event, and due to that, they are commonly referred to as synaptopathies. The exact mechanisms of synapse dysfunction in the different diseases are not well understood and their study would help understanding the pathogenic role of synaptic degeneration, as well as differences and commonalities among them and highlight candidate synaptic biomarkers for specific disorders. The assessment of synaptic proteins in cerebrospinal fluid (CSF), which can reflect synaptic dysfunction in patients with cognitive disorders, is a keen area of interest. Substantial research efforts are now directed toward the investigation of CSF synaptic pathology to improve the diagnosis of neurodegenerative disorders at an early stage as well as to monitor clinical progression. In this review, we will first summarize the pathological events that lead to synapse loss and then discuss the available data on established (eg, neurogranin, SNAP-25, synaptotagmin-1, GAP-43, and α-syn) and emerging (eg, synaptic vesicle glycoprotein 2A and neuronal pentraxins) CSF biomarkers for synapse dysfunction, while highlighting possible utilities, disease specificity, and technical challenges for their detection.","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2020-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1177271920950319","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38368135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 64

Simple Methods for Evaluating 4 Types of Biomarkers: Surrogate Endpoint, Prognostic, Predictive, and Cancer Screening. 评估4种生物标志物的简单方法:替代终点、预后、预测和癌症筛查。

IF 3.8

Biomarker Insights Pub Date : 2020-08-04 eCollection Date: 2020-01-01 DOI: 10.1177/1177271920946715

Stuart G Baker, Barnett S Kramer

引用次数: 3