Expert Opinion on Orphan Drugs最新文献_第10页

The potential of gene therapy for mucopolysaccharidosis type I I型粘多糖病基因治疗的潜力

IF 0.8 4区医学

Expert Opinion on Orphan Drugs Pub Date : 2020-01-02 DOI: 10.1080/21678707.2020.1715208

Luisa Natalia Pimentel Vera, G. Baldo

{"title":"The potential of gene therapy for mucopolysaccharidosis type I","authors":"Luisa Natalia Pimentel Vera, G. Baldo","doi":"10.1080/21678707.2020.1715208","DOIUrl":"https://doi.org/10.1080/21678707.2020.1715208","url":null,"abstract":"ABSTRACT Introduction: Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disorder caused by mutations in the IDUA gene, characterized by deficient IDUA enzyme production and storage of glycosaminoglycans in tissues. Currently, therapeutic strategies approved have shown an improvement in quality of life of patients, but the majority of severe symptoms including cognitive and skeletal alterations persist. Gene therapy aimed to correct the genetic defect holds promise. Indeed, preclinical results show that it may be possible to develop a gene therapy strategy that may overcome the present limitations. In this review, authors review studies involving gene therapy for MPS I in the last years and highlight the most promising approaches. Areas covered: Authors review main studies involving gene therapy and genome editing for MPS I in the last 2–3 decades, from the initial in vitro studies up to the first clinical trials, and prospect what the future may hold for this technology in this disease. Expert opinion: Among all strategies studied, viral gene therapy and genome editing are being applied in clinical trials. Some of the results are inconclusive while scaling the process from animal models to human. The key for better outcomes relies on giving patients a proper therapy.","PeriodicalId":12118,"journal":{"name":"Expert Opinion on Orphan Drugs","volume":null,"pages":null},"PeriodicalIF":0.8,"publicationDate":"2020-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678707.2020.1715208","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41928325","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}

引用次数: 4

Monitoring progression of retinitis pigmentosa: current recommendations and recent advances. 监测视网膜色素变性的进展:目前的建议和最新进展。

IF 0.8 4区医学

Expert Opinion on Orphan Drugs Pub Date : 2020-01-01 Epub Date: 2020-03-02 DOI: 10.1080/21678707.2020.1735352

Moreno Menghini, Jasmina Cehajic-Kapetanovic, Robert E MacLaren

{"title":"Monitoring progression of retinitis pigmentosa: current recommendations and recent advances.","authors":"Moreno Menghini, Jasmina Cehajic-Kapetanovic, Robert E MacLaren","doi":"10.1080/21678707.2020.1735352","DOIUrl":"10.1080/21678707.2020.1735352","url":null,"abstract":"ABSTRACT Introduction: Retinitis pigmentosa (RP) is the most common form of inherited retinal degenerations with an estimated prevalence of 1 in 4,000 and more than 1 million individuals affected worldwide. With the introduction of the first retinal gene therapy in 2017, the importance of understanding the mechanisms of retinal degeneration and its natural progression has shifted from being of academic interest to being of pivotal for the development of new therapies. Areas covered: This review covers standard and innovative diagnostic techniques and complementary examinations needed for the evaluation and treatment of RP. It includes chapters on the assessment of visual function, retinal morphology, and genotyping. Expert opinion: Monitoring the progression of RP can best be achieved by combining assessments of both visual function and morphology. Visual acuity testing using ETDRS charts should be complemented by low-luminance visual acuity and color vision tests. Assessment of the visual field can also be useful in less advanced cases. In those with central RP involvement measuring retinal sensitivity using microperimetry is recommended. Retinal morphology is best assessed by OCT and autofluorescence. Genetic testing is pivotal as it contributes to the pathophysiological understanding and can guide clinical management as well as identify individuals that could benefit from retinal gene therapy.","PeriodicalId":12118,"journal":{"name":"Expert Opinion on Orphan Drugs","volume":null,"pages":null},"PeriodicalIF":0.8,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678707.2020.1735352","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9147880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 28

The future of gene-targeted therapy for hereditary tyrosinemia type 1 as a lead indication among the inborn errors of metabolism. 基因靶向治疗遗传性1型酪氨酸血症作为先天性代谢错误的主要指征的未来。

IF 0.8 4区医学

Expert Opinion on Orphan Drugs Pub Date : 2020-01-01 Epub Date: 2020-07-21 DOI: 10.1080/21678707.2020.1791082

Whitney S Thompson, Gourish Mondal, Caitlin J Vanlith, Robert A Kaiser, Joseph B Lillegard

{"title":"The future of gene-targeted therapy for hereditary tyrosinemia type 1 as a lead indication among the inborn errors of metabolism.","authors":"Whitney S Thompson, Gourish Mondal, Caitlin J Vanlith, Robert A Kaiser, Joseph B Lillegard","doi":"10.1080/21678707.2020.1791082","DOIUrl":"https://doi.org/10.1080/21678707.2020.1791082","url":null,"abstract":"Introduction: Inborn errors of metabolism (IEMs) often result from single-gene mutations and collectively cause liver dysfunction in neonates leading to chronic liver and systemic disease. Current treatments for many IEMs are limited to maintenance therapies that may still require orthotropic liver transplantation. Gene therapies offer a potentially superior approach by correcting or replacing defective genes with functional isoforms; however, they face unique challenges from complexities presented by individual diseases and their diverse etiology, presentation, and pathophysiology. Furthermore, immune responses, off-target gene disruption, and tumorigenesis are major concerns that need to be addressed before clinical application of gene therapy.Areas covered: The current treatments for IEMs are reviewed as well as the advances in, and barriers to, gene therapy for IEMs. Attention is then given to ex vivo and in vivo gene therapy approaches for hereditary tyrosinemia type 1 (HT1). Of all IEMs, HT1 is particularly amenable to gene therapy because of a selective growth advantage conferred to corrected cells, thereby lowering the initial transduction threshold for phenotypic relevance.Expert opinion: It is proposed that not only is HT1 a safe indication for gene therapy, its unique characteristics position it to be an ideal IEM to develop for clinical investigation.","PeriodicalId":12118,"journal":{"name":"Expert Opinion on Orphan Drugs","volume":null,"pages":null},"PeriodicalIF":0.8,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678707.2020.1791082","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38736749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 9

Inhibiting inflammatory cytokines in adult onset Still’s disease. Current trends and new therapeutic perspectives 在成人斯蒂尔病中抑制炎性细胞因子。当前趋势和新的治疗前景

IF 0.8 4区医学

Expert Opinion on Orphan Drugs Pub Date : 2019-12-02 DOI: 10.1080/21678707.2019.1701431

P. Ruscitti, A. Conforti, V. Pavlych, R. Giacomelli

{"title":"Inhibiting inflammatory cytokines in adult onset Still’s disease. Current trends and new therapeutic perspectives","authors":"P. Ruscitti, A. Conforti, V. Pavlych, R. Giacomelli","doi":"10.1080/21678707.2019.1701431","DOIUrl":"https://doi.org/10.1080/21678707.2019.1701431","url":null,"abstract":"ABSTRACT Introduction: Multiple lines of evidence suggest the clinical usefulness of inhibiting inflammatory cytokines in patients affected by adult onset Still’s disease (AOSD), a rare inflammatory disease. The lack of response to the first therapeutic strategy with glucocorticoids and synthetic disease-modifying anti-rheumatic drugs (DMARDs) identifies ‘refractory patients’, to be subsequently treated with biologic DMARDs. Areas covered: In this article, evidence has been reviewed about the clinical usefulness of biologic DMARDs, targeting inflammatory cytokines, in AOSD, analyzing current trends and suggesting future therapeutic perspectives. Expert opinion: Therapeutic management of AOSD is directed at targeting inflammatory signs and symptoms, preventing life-threating complications, and minimizing the adverse effects of immunosuppressive therapies. In this context, over the last decade, the clinical usefulness of inhibiting inflammatory cytokines has shown in AOSD with multiple benefits, since a large percentage of patients attain a clinical response. The inhibition of inflammatory cytokines could also be helpful in managing life-threating complications of AOSD. Going forward, this field of research is rapidly growing, and in the next future, the results about ongoing randomized controlled trials and the development of clinical tools readily transferable in clinical practice, would improve the management of AOSD providing more targeted treatment and improving the outcomes of these patients.","PeriodicalId":12118,"journal":{"name":"Expert Opinion on Orphan Drugs","volume":null,"pages":null},"PeriodicalIF":0.8,"publicationDate":"2019-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678707.2019.1701431","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47461550","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}

引用次数: 0

The senseless orphanage of Chagas disease 恰加斯病的孤儿院

IF 0.8 4区医学

Expert Opinion on Orphan Drugs Pub Date : 2019-12-02 DOI: 10.1080/21678707.2019.1701432

C. Alonso-Vega, Irene Losada-Galván, M. Pinazo, Javier Sancho Mas, J. G. Brustenga, J. Alonso-Padilla

{"title":"The senseless orphanage of Chagas disease","authors":"C. Alonso-Vega, Irene Losada-Galván, M. Pinazo, Javier Sancho Mas, J. G. Brustenga, J. Alonso-Padilla","doi":"10.1080/21678707.2019.1701432","DOIUrl":"https://doi.org/10.1080/21678707.2019.1701432","url":null,"abstract":"ABSTRACT Introduction: Chagas disease is caused by the parasite Trypanosoma cruzi. Endemic in 21 American countries, there are ~7 million people infected, of which 14,000 die every year. Despite this burden, Chagas remains an orphan disease as it mainly affects poor communities with low economic and political power. Areas covered: There are two drugs available to treat the infection, but both have safety and efficacy issues. Investment in new treatments and other control measures has been historically neglected. This trend is changing and there are novel perspectives to put an end to this senseless orphanage. Research and development agenda of new therapies, diagnostic tools and biomarkers have moved forward during the last decade; and patients associations have been active in promoting awareness of the disease all along. Besides, the WHO recently declared April 14th as the ‘World Chagas disease day’, which will increase the visibility of the disease and attract attention internationally. Expert opinion: Efforts must focus on the prevention of new infections, but also in the management of the millions already chronically infected. This will require an integral approach where increasing the number of trained health workers and generalizing access to diagnosis and treatment will be fundamental.","PeriodicalId":12118,"journal":{"name":"Expert Opinion on Orphan Drugs","volume":null,"pages":null},"PeriodicalIF":0.8,"publicationDate":"2019-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678707.2019.1701432","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47991539","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}

引用次数: 5

An update on the progress of preclinical models for guiding therapeutic management of neuronal ceroid lipofuscinosis 指导神经元类脂褐质病治疗管理的临床前模型进展

IF 0.8 4区医学

Expert Opinion on Orphan Drugs Pub Date : 2019-12-02 DOI: 10.1080/21678707.2019.1703672

Hemanth R. Nelvagal, J. Cooper

{"title":"An update on the progress of preclinical models for guiding therapeutic management of neuronal ceroid lipofuscinosis","authors":"Hemanth R. Nelvagal, J. Cooper","doi":"10.1080/21678707.2019.1703672","DOIUrl":"https://doi.org/10.1080/21678707.2019.1703672","url":null,"abstract":"ABSTRACT Introduction: The neuronal ceroid lipofuscinoses (NCLs) are a group of pediatric inherited neurodegenerative disorders affecting children and young adults. All forms of NCL are fatal and with no curative therapies available there is a pressing need to model their pathology in biological model systems to enable the systematic and rigorous testing of preclinical therapies. Areas covered: This article discusses and provides an update on the recent advances in modelling NCL disease pathology in various different model systems and their relevance to testing preclinical therapies so as to ensure optimal translation into human patients. The research articles discussed here were curated from PubMed (Last accessed-12.4.19) and Google Scholar (Last access-12.4.19) databases. Expert opinion: Both in vitro and in vivo biological model systems have been established for various forms of NCL. These have informed us about pathophysiology, revealed novel therapeutic targets, and provided landmarks of disease progression against which to test potential therapies. Studying NCL pathology across different species has been very informative regarding where therapies need to be delivered with an increasing focus on disease outside the brain. Testing such therapies in animal models of increasing complexity has allowed the translation of more efficacious therapies for clinical trials.","PeriodicalId":12118,"journal":{"name":"Expert Opinion on Orphan Drugs","volume":null,"pages":null},"PeriodicalIF":0.8,"publicationDate":"2019-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678707.2019.1703672","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48597249","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}

引用次数: 0

Pharmacological therapy in a rare disease: challenges in the long-term management of granulomatosis with polyangiitis 一种罕见疾病的药物治疗：肉芽肿伴多血管炎长期治疗的挑战

IF 0.8 4区医学

Expert Opinion on Orphan Drugs Pub Date : 2019-12-02 DOI: 10.1080/21678707.2019.1701433

J. Sultana, N. Azzopardi-Muscat, B. Coleiro, L. Grech, M. Muscat, D. Santoro, G. Trifirò

引用次数: 2

Variability in management and outcomes of therapy with eculizumab in atypical hemolytic uremic syndrome 异珠单抗治疗非典型溶血性尿毒症综合征的管理和结果的可变性

IF 0.8 4区医学

Expert Opinion on Orphan Drugs Pub Date : 2019-12-02 DOI: 10.1080/21678707.2019.1703108

E. García-Martín, S. Manrique-Rodríguez, C. Martínez Fernández-Llamazares, Marian Goicoechea-Diezhondino, Olalla Álvarez-Blanco, M. García-Morin, M. Sanjurjo-Sáez

{"title":"Variability in management and outcomes of therapy with eculizumab in atypical hemolytic uremic syndrome","authors":"E. García-Martín, S. Manrique-Rodríguez, C. Martínez Fernández-Llamazares, Marian Goicoechea-Diezhondino, Olalla Álvarez-Blanco, M. García-Morin, M. Sanjurjo-Sáez","doi":"10.1080/21678707.2019.1703108","DOIUrl":"https://doi.org/10.1080/21678707.2019.1703108","url":null,"abstract":"ABSTRACT Objectives: Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy caused by complement dysregulation. The aim of this study was to establish the efficacy and safety of eculizumab in patients with aHUS in clinical practice and to describe different individualization strategies. Methods: Authors performed an observational, longitudinal, and ambispective study at a tertiary care center. Clinical histories of patients in treatment with eculizumab were reviewed. Effectiveness and safety were assessed with the evolution of analytical parameters, symptoms and concomitant therapies required. Results: Authors included five patients (two children). The patients were followed up from diagnosis and first administration of eculizumab. Four patients discontinued eculizumab: one because he had anti-factor H autoantibodies that could be managed with immunosuppressive therapy, another because of non-response, and the other two because of clinical stabilization, resolution of TMA, and no findings of high-risk mutations in complement factors. Therapy was tapered in the remaining patients in aHUS remission. No adverse events were identified during or after treatment. Conclusion: Eculizumab is an effective and safe treatment for patients diagnosed with primary or secondary aHUS. Personalized treatment, tapering or discontinuation should be taken on an individual basis by a multidisciplinary team in order to increase the cost-effectiveness of this therapy.","PeriodicalId":12118,"journal":{"name":"Expert Opinion on Orphan Drugs","volume":null,"pages":null},"PeriodicalIF":0.8,"publicationDate":"2019-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678707.2019.1703108","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45587277","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}

引用次数: 0

Sydenham’s chorea: an update on pathophysiology, clinical features and management 西德纳姆舞蹈病:病理生理学、临床特征和治疗的最新进展

IF 0.8 4区医学

Expert Opinion on Orphan Drugs Pub Date : 2019-11-02 DOI: 10.1080/21678707.2019.1684259

L. Vasconcelos, M. Vasconcelos, M. C. Nunes, A. Teixeira

引用次数: 6

Duodenal adenocarcinoma: neoadjuvant and adjuvant therapy strategies 十二指肠腺癌：新辅助和辅助治疗策略

IF 0.8 4区医学

Expert Opinion on Orphan Drugs Pub Date : 2019-11-02 DOI: 10.1080/21678707.2019.1684257

A. Dave, Jason T. Wiseman, J. Cloyd

{"title":"Duodenal adenocarcinoma: neoadjuvant and adjuvant therapy strategies","authors":"A. Dave, Jason T. Wiseman, J. Cloyd","doi":"10.1080/21678707.2019.1684257","DOIUrl":"https://doi.org/10.1080/21678707.2019.1684257","url":null,"abstract":"ABSTRACT Introduction: Duodenal adenocarcinoma (DA) is a relatively rare gastrointestinal malignancy associated with poor outcomes. The mainstay of treatment is surgical resection with regional lymphadenectomy but recurrence rates remain high. Due to the relatively low incidence of DA, the lack of randomized controlled trials, and its inclusion with heterogeneous groups of periampullary and other small bowel cancers, strong evidence for the use of neoadjuvant or adjuvant treatment approaches is lacking. Areas covered: The purpose of this article is to review the existing literature on neoadjuvant and adjuvant therapy options along with surgical options for patients with DA. Expert opinion: The primary management of localized DA is surgical resection with negative margins and regional lymphadenectomy. Adjuvant therapy should be recommended for all patients with high-risk pathologic features such as positive lymph nodes or microscopically positive margins. The use of neoadjuvant therapy should be reserved for those patients with locally advanced disease who require downstaging to facilitate resectability. Nevertheless, given the relative rarity of DA, the available literature to guide optimal multimodality treatment decisions is minimal and additional research is needed. In the meantime, patients with DA should be treated at experienced tertiary centers by multidisciplinary oncology teams.","PeriodicalId":12118,"journal":{"name":"Expert Opinion on Orphan Drugs","volume":null,"pages":null},"PeriodicalIF":0.8,"publicationDate":"2019-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678707.2019.1684257","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45998148","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}

引用次数: 1