Rare disease and orphan drugs journal最新文献

{"title":"2017-2023: state of the art of gene therapies in rare diseases in Europe: the dynamics of clinical R&D, new approved treatments and expected therapies in the pipelines","authors":"Tristan Gicquel, Lucas Cortial, Karyna Lutsyk, Sylvain Forget, Serge Braun, Pierre-Olivier Boyer, Vincent Laugel, Olivier Blin","doi":"10.20517/rdodj.2023.29","DOIUrl":"https://doi.org/10.20517/rdodj.2023.29","url":null,"abstract":"Aim: Gene therapies have been tested over the past three decades, and after a first market authorization in 2017, the field is starting to deliver. The study aims to analyze the current development dynamics of gene therapies for rare diseases using the GENOTRIAL database®, which gathers information on gene therapy clinical trials and studies conducted between 2017 and 2023 in Europe. Methods: The study involved extracting and filtering clinical trial data from the EudraCT database. Trials with the keyword \"Gene Therapy\" were selected and filtered using the \"Rare disease\" filter. Manual verification was conducted to ensure that the selected trial only concerned gene therapy treatments authorized in Europe for rare diseases in phases I to III. A total of 300 European country-related clinical investigations representing a total of 93 European-specific clinical studies were included in the GENOTRIAL database. The trials were classified by development phases, temporal status, sponsors and investigating countries, rare diseases with their related therapeutic area, and approval regulatory information of the identified gene therapies. Results: Analysis reveals that rare diseases present a promising area for gene therapy development. On average, eight rare disease gene therapy trials are launched each year in Europe. The main sponsors of European clinical trials of gene therapies for rare diseases are from US, followed by the United Kingdom and France. The United Kingdom conducts the highest number of investigations in Europe, followed by France, Italy, Spain, and Germany. Nutritional and metabolic diseases are the most represented therapeutic area, followed by rare oncology, blood and lymphatic diseases, and ocular diseases. The analysis identifies 73 gene therapy medical products covering 35 diseases at various stages of development, with 12 new therapies approved in recent years for 8 rare diseases, while 15 other gene therapies are at an advanced stage of phase III in their development plan for 11 other rare diseases. Conclusion: Gene therapy has shown significant progress and potential in treating rare genetic diseases. Europe has emerged as a promising region for gene therapy clinical trials in rare diseases. Efforts are now required to catch up with the USA and UK regarding the number of clinical trials sponsored by European groups.","PeriodicalId":74638,"journal":{"name":"Rare disease and orphan drugs journal","volume":"6 3","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135868797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Federated learning for rare disease detection: a survey","authors":"Jiaqi Wang, Fenglong Ma","doi":"10.20517/rdodj.2023.16","DOIUrl":"https://doi.org/10.20517/rdodj.2023.16","url":null,"abstract":"The detection of rare diseases utilizing advanced artificial intelligence (AI) techniques has garnered considerable attention in recent years. Numerous approaches have been proposed to detect diverse rare diseases by leveraging a range of medical data, including medical images, electronic health records, and sensory data. In order to safeguard the privacy of health data, considerable investigation has been undertaken on a novel learning paradigm known as federated learning, which has been applied to the domain of rare disease detection. Nonetheless, this nascent research direction remains in its infancy, necessitating greater scrutiny and attention. Within this survey, our primary focus lies in providing fresh perspectives, deliberating the challenges, and enumerating potential research directions concerning the application of federated learning techniques in rare disease detection. Furthermore, we provide a succinct summary of existing advancements using AI techniques for rare disease detection, as well as the utilization of federated learning within healthcare informatics. Moreover, we furnish a compilation of publicly available datasets that can be employed to validate novel federated learning algorithms for the purpose of detecting rare diseases.","PeriodicalId":74638,"journal":{"name":"Rare disease and orphan drugs journal","volume":"9 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136254377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factors influencing pulmonary arterial pressure in three related patients with Cantú syndrome: glyburide may provide precision care","authors":"Ronald W. Day, Benjamin F. Call","doi":"10.20517/rdodj.2023.12","DOIUrl":"https://doi.org/10.20517/rdodj.2023.12","url":null,"abstract":"A range of pulmonary arterial pressures was observed in three related patients with Cantú syndrome. The incident patient developed a moderately high pulmonary vascular resistance. Several factors influenced the severity of his pulmonary vascular disease and the events, which ultimately resulted in his death. However, he had an acute improvement in blood pressure and respiratory support after a single dose of glyburide when he was critically ill. The father and sister of the incident patient have evidence of mildly increased pulmonary arterial pressure with normal pulmonary vascular resistance. They are being treated with glyburide to potentially decrease the high cardiac output associated with a gain in KATP channel function. Additional experience with glyburide or other KATP channel inhibitors is needed to determine the most appropriate agent, dose, time, and duration of treatment for patients with Cantú syndrome.","PeriodicalId":74638,"journal":{"name":"Rare disease and orphan drugs journal","volume":"16 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135344166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Next-generation sequencing-based newborn screening initiatives in Europe: an overview","authors":"Virginie Bros-Facer, Stacie Taylor, Christine Patch","doi":"10.20517/rdodj.2023.26","DOIUrl":"https://doi.org/10.20517/rdodj.2023.26","url":null,"abstract":"Aim: This article describes results from a survey targeting healthcare professionals (HCPs) leading newborn screening (NBS) initiatives in Europe. The survey was developed within the framework of a dedicated working group set up by the International Rare Diseases Research Consortium (IRDiRC) to gather collective efforts relating to NBS. The objectives of the survey were to gain a better understanding of approaches being tested for the expansion of NBS and to raise awareness of the significant momentum across Europe to evaluate novel technologies for use in future NBS programs. Methods: A web-based survey including 57 questions was developed to gather information about genomic newborn screening initiatives in Europe that are using next-generation sequencing (NGS) as a first-tier test. Responses were analyzed qualitatively, and aggregated results are presented herein. The identity of some initiatives is not presented to preserve confidentiality. Results: The findings of the survey indicated that most initiatives are in the planning stage and have not yet started. Although all 14 studies are heterogeneous in design, there is broad consensus that NGS approaches to NBS will, in the short term, be implemented in parallel with current screening programs. The results of this survey can be used to inform the design of studies still in the early planning stages. Conclusion: Here, we provide an overview of NGS-based initiatives in Europe. Importantly, the initiatives described herein will generate evidence to evaluate the utility and feasibility of NGS approaches to NBS, thereby shortening the pathway to responsible implementation of NGS in NBS and informing future research efforts.","PeriodicalId":74638,"journal":{"name":"Rare disease and orphan drugs journal","volume":"18 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135344963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Could federated data analysis be the catalyst accelerating the introduction of newborn genome screening for the detection of genetic disease?","authors":"Petros Tsipouras, Maria Chatzou Dunford, Hadley Sheppard, Hannah Gaimster, Theoklis Zaoutis","doi":"10.20517/rdodj.2023.15","DOIUrl":"https://doi.org/10.20517/rdodj.2023.15","url":null,"abstract":"Data federation intermediated through trusted research environments can help accelerate the adoption and utilization of newborn genome screening worldwide. Data federation will protect individual datasets from unauthorized security breaches, allow analysis in situ , and bypass the need for cumbersome data sharing agreements between parties. Finally, data federation could accelerate the adoption of new therapies for rare genetic diseases with the use of synthetic clinical trials.","PeriodicalId":74638,"journal":{"name":"Rare disease and orphan drugs journal","volume":"82 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135537850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular mechanisms for targeted treatments in fragile X syndrome","authors":"Isabel Miranda, Randi Hagerman","doi":"10.20517/rdodj.2023.21","DOIUrl":"https://doi.org/10.20517/rdodj.2023.21","url":null,"abstract":"Fragile X syndrome (FXS) is caused by a full mutation (> 200 repeats) in the 5’untranslated region of the Fragile X Messenger Ribonucleoprotein 1 gene (FMR1 gene), which leads to methylation and silencing of expression, generating the total or partial absence of its product, FMR1 protein (FMRP). When the repetitions are between 55 and 200 cytosine-guanine-guanine (CGG) repeats, it is called a premutation, which is related to a wide spectrum of conditions such as Fragile X-associated tremor ataxia syndrome (FXTAS), fragile X-associated primary ovarian insufficiency (FXPOI), and fragile X-associated neuropsychiatric disorders (FXAND). High levels of FMR1 mRNA are implicated in premutation pathophysiology, which differs from the deficiency or absence of FMRP in FXS. In recent years, numerous attempts have been made to find treatments that can counteract the effects of the absence of FMRP and improve symptoms associated with the condition such as intellectual disability, anxiety, autism, stereotypies, language delay, and aggressive behavior. Here, we review current treatments in addition to targeted treatments that can reverse some of the neurobiological abnormalities in those with FXS. We also review molecular interventions that will hopefully lead to a promising future for those affected by FXS and their families.","PeriodicalId":74638,"journal":{"name":"Rare disease and orphan drugs journal","volume":"184 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135354010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of newborn screening policies in Spain 2003-2022: what do we actually need to reach an agreement?","authors":"Cristina Valcárcel-Nazco, Lidia García-Pérez, Renata Linertová, Carmen Guirado-Fuentes, Aránzazu Hernández-Yumar, Lucinda Paz-Valiñas, Paula Cantero-Muñoz, Manuel Posada, Pedro Serrano-Aguilar","doi":"10.20517/rdodj.2023.14","DOIUrl":"https://doi.org/10.20517/rdodj.2023.14","url":null,"abstract":"Newborn screening (NBS) for inherited disorders is recognized as an essential public health intervention to improve health outcomes in the newborn population. The implementation of an NBS programme requires an evaluation of effectiveness, safety, cost-effectiveness, feasibility, and budget impact. Determining which of the known disorders should be included in NBS programmes is a public health policy challenge. In this context, economic evaluation aims to contribute to the sustainability of public health systems, but the appropriate economic evaluation framework for these interventions is still unclear. Existing NBS programmes vary widely in the number and type of disorders screened, even among the most developed European countries, despite the fact that the core criteria for guiding policy decision-making are standard. In Spain, where delivery of NBS programmes is marked by heterogeneity between regions, guidelines based on the best available scientific evidence are being established in order to achieve standardization of NBS policies and programmes at a national level. This paper provides a general overview of existing evidence-based health-policy initiatives aimed at enhancing the equity and efficiency of the NBS programme in Spain and their impact on health decisions. We also describe existing challenges to reduce uncertainty, and the variations observed in decisions relating to the content and procedures used in NBS programmes.","PeriodicalId":74638,"journal":{"name":"Rare disease and orphan drugs journal","volume":"35 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134990581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A systematic review of real-world applications of genome sequencing for newborn screening","authors":"Giuditta Magnifico, I. Artuso, S. Benvenuti","doi":"10.20517/rdodj.2023.17","DOIUrl":"https://doi.org/10.20517/rdodj.2023.17","url":null,"abstract":"Aim: With the costs of genomic sequencing falling quickly and an ever-increasing number of clinical laboratories equipped with new-generation sequencing machines, healthcare systems around the world are getting ready to enter the era of genomic newborn screening (NBS). However, the adoption of Genomic Sequencing (GS), encompassing whole-exome sequencing (WES) and whole-genome sequencing (WGS), in NBS programs raises a number of clinical, ethical, and legal questions as well as organizational and economic challenges. This systematic review is part of a feasibility study to assess the introduction of WGS for NBS in Lombardy region with the specific aim of gathering evidence from existing pilots in the field whose results have been published. \u0000 Methods: Three different sources were identified for the selection of articles in order to obtain a various and unbiased set of publications. 33 articles were retained for analysis to answer the following questions: 1. Clinical: Does genomic sequencing demonstrate clinical utility in the context of NBS? What are the limitations of these kind of programs? 2. Societal: What are the social, ethical and psychological implications of using GS for NBS? 3. Governance: What are the legal, economic, and organizational challenges for GS-based NBS programs? \u0000 Results: There is a general consensus in the literature on the key principles that should guide the adoption of GS in NBS, such as the inclusion of actionable genes only, the need for informed consent from the parents, the right of the newborn to an open future, which means the exclusion of late-onset diseases even when those are considered treatable. However, there are still several differences in how these principles are detailed and applied. \u0000 Conclusion: Real-world evidence from a handful of pilot projects (namely BabySeq and NC-Nexus, both carried out in the USA) have been published recently; however, this evidence is not yet sufficient to put an end to the broad and animated debate on the use of GS for NBS. Ethical, legal, and social issues still constitute great challenges and major barriers to wide and uniform adoption of GS in NBS. On the clinical side, a number of issues remain unaddressed, such as the benefits and limitations of the different approaches (targeted sequencing, GS only versus GS+standard NBS), the genes/diseases to include and the frequency of incidental findings, identification of carrier status, and variants of uncertain significance (VUS). Further pilots and consultations with involved stakeholders will be necessary before GS-based NBS can be accepted and systematically implemented in national healthcare programs.","PeriodicalId":74638,"journal":{"name":"Rare disease and orphan drugs journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43726086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cathepsin C: structure, function, and pharmacological targeting","authors":"Milena Stojkovska Docevska, Marko Novinec","doi":"10.20517/rdodj.2023.09","DOIUrl":"https://doi.org/10.20517/rdodj.2023.09","url":null,"abstract":"Cathepsin C is a papain-like cysteine peptidase known primarily for its involvement in the activation of serine peptidases in neutrophils and other immune cells. Its critical role in this process qualifies cathepsin C as a target for the treatment of inflammatory diseases, and its most advanced inhibitor, brensocatib (Insmed), is currently in phase 3 clinical trials for the treatment of non-cystic fibrosis bronchiectasis. Beyond neutrophils, its importance is highlighted by loss-of-function mutations that cause the recessively inherited Papillon-Lefèvre syndrome. At the molecular level, cathepsin C has several structural and functional features that set it apart from other members of the family and enable its selective targeting. It possesses dipeptidyl-peptidase activity (its other common name is dipeptidyl-peptidase I) due to the presence of an additional exclusion domain that also controls its stepwise tetramerization during maturation. In this review article, we summarize the current state of the art regarding the biochemical properties of cathepsin C, its physiological and pathological roles in neutrophils and beyond, and recent advances in the development and evaluation of cathepsin C inhibitors.","PeriodicalId":74638,"journal":{"name":"Rare disease and orphan drugs journal","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41262337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutrophil serine proteases","authors":"Marcin Skoreński, Karolina Torzyk, M. Sieńczyk","doi":"10.20517/rdodj.2022.21","DOIUrl":"https://doi.org/10.20517/rdodj.2022.21","url":null,"abstract":"The identification and characterization of the four active neutrophil serine proteases (NSPs) have provided a better understanding of their roles in various physiological and pathological processes. The availability of appropriate tools such as substrates, inhibitors, and activity-based probes (ABPs) for studying their activity and functions in cells has become increasingly important. In this paper, the authors provide a comprehensive overview of the current state of knowledge on the tools available for studying NSPs. The substrates, inhibitors, and ABPs that have been developed to date are described, including their strengths and limitations. The authors also discuss the potential implications of these tools for future research on NSPs, including their potential use in the development of new therapeutics for various diseases. Overall, this paper highlights the importance of understanding the activity and functions of NSPs and provides valuable information on the tools available for studying these proteases.","PeriodicalId":74638,"journal":{"name":"Rare disease and orphan drugs journal","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67659854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}