Gene Therapy最新文献_第7页

Approval and therapeutic value of gene therapies in the US and Europe 基因疗法在美国和欧洲的批准和治疗价值。

IF 5.1 3区医学

Gene Therapy Pub Date : 2023-11-08 DOI: 10.1038/s41434-023-00402-4

Kerstin N. Vokinger, Camille E. G. Glaus, Aaron S. Kesselheim

{"title":"Approval and therapeutic value of gene therapies in the US and Europe","authors":"Kerstin N. Vokinger, Camille E. G. Glaus, Aaron S. Kesselheim","doi":"10.1038/s41434-023-00402-4","DOIUrl":"10.1038/s41434-023-00402-4","url":null,"abstract":"Gene therapies are a fast-growing area of innovation and hold promise for the treatment of many diseases currently with unmet medical need. To better understand the clinical importance of the current landscape of approved gene therapies, we conducted a systematic analysis of the approved gene therapies and their added therapeutic value. Through December 2022, 13 gene therapies have been approved in the US, 15 in the EU, and 9 in Switzerland. Nine gene therapies have been approved in all three jurisdictions, and 11 in both the US and EU. Among the 11 gene therapies approved in more than one jurisdiction, there were differences in the approved indications among the regulatory agencies, mostly the European drug agencies (EMA and Swissmedic) being more restrictive. Among the gene therapies with available therapeutic ratings, approximately two-thirds had high added therapeutic value, which is substantially higher than the average prevalence of high added therapeutic value ratings among new drugs and biologics (approximately one-third). However, therapies with high added therapeutic value will not be useful for patients if excessive prices limit access to them. Drug pricing reforms should address gene therapies to ensure access to new gene therapies that can offer important therapeutic value to patients.","PeriodicalId":12699,"journal":{"name":"Gene Therapy","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71480725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Towards affordable CRISPR genomic therapies: a task force convened by the Innovative Genomics Institute 实现负担得起的CRISPR基因组疗法：创新基因组研究所召集的一个工作组。

IF 5.1 3区医学

Gene Therapy Pub Date : 2023-11-08 DOI: 10.1038/s41434-023-00392-3

Lea Witkowsky, Matthew Norstad, Audrey R. Glynn, Melinda Kliegman

引用次数: 0

The estimated annual financial impact of gene therapy in the United States 基因治疗在美国的年度财务影响估计。

IF 5.1 3区医学

Gene Therapy Pub Date : 2023-11-08 DOI: 10.1038/s41434-023-00419-9

Chi Heem Wong, Dexin Li, Nina Wang, Jonathan Gruber, Andrew W. Lo, Rena M. Conti

{"title":"The estimated annual financial impact of gene therapy in the United States","authors":"Chi Heem Wong, Dexin Li, Nina Wang, Jonathan Gruber, Andrew W. Lo, Rena M. Conti","doi":"10.1038/s41434-023-00419-9","DOIUrl":"10.1038/s41434-023-00419-9","url":null,"abstract":"Gene therapy is a new class of medical treatment that alters part of a patient’s genome through the replacement, deletion, or insertion of genetic material. While still in its infancy, gene therapy has demonstrated immense potential to treat and even cure previously intractable diseases. Nevertheless, existing gene therapy prices are high, raising concerns about its affordability for U.S. payers and its availability to patients. We assess the potential financial impact of novel gene therapies by developing and implementing an original simulation model which entails the following steps: identifying the 109 late-stage gene therapy clinical trials underway before January 2020, estimating the prevalence and incidence of their corresponding diseases, applying a model of the increase in quality-adjusted life years for each therapy, and simulating the launch prices and expected spending of all available gene therapies annually. The results of our simulation suggest that annual spending on gene therapies will be approximately $20.4 billion, under conservative assumptions. We decompose the estimated spending by treated age group as a proxy for insurance type, finding that approximately one-half of annual spending will on the use of gene therapies to treat non-Medicare-insured adults and children. We conduct multiple sensitivity analyses regarding our assumptions and model parameters. We conclude by considering the tradeoffs of different payment methods and policies that intend to ensure patient access to the expected benefits of gene therapy.","PeriodicalId":12699,"journal":{"name":"Gene Therapy","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10678302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71480728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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: 0

A practical approach for adoption of a hub and spoke model for cell and gene therapies in low- and middle-income countries: framework and case studies 在低收入和中等收入国家采用细胞和基因治疗中心辐射模型的实用方法：框架和案例研究。

IF 5.1 3区医学

Gene Therapy Pub Date : 2023-10-30 DOI: 10.1038/s41434-023-00425-x

Shadi Saleh, Omar Dabbous, Sean D. Sullivan, Dipen Ankleshwaria, Daiane Trombini, Mondher Toumi, Mahmoud Diaa, Anish Patel, Burcu Kazazoglu Taylor, Sean Tunis

{"title":"A practical approach for adoption of a hub and spoke model for cell and gene therapies in low- and middle-income countries: framework and case studies","authors":"Shadi Saleh, Omar Dabbous, Sean D. Sullivan, Dipen Ankleshwaria, Daiane Trombini, Mondher Toumi, Mahmoud Diaa, Anish Patel, Burcu Kazazoglu Taylor, Sean Tunis","doi":"10.1038/s41434-023-00425-x","DOIUrl":"10.1038/s41434-023-00425-x","url":null,"abstract":"In the rapidly evolving landscape of biotechnologies, cell and gene therapies are being developed and adopted at an unprecedented pace. However, their access and adoption remain limited, particularly in low- and middle-income countries (LMICs). This study aims to address this critical gap by exploring the potential of applying a hub and spoke model for cell and gene therapy delivery in LMICs. We establish the identity and roles of relevant stakeholders, propose a hub and spoke model for cell and gene therapy delivery, and simulate its application in Brazil and the Middle East and North Africa. The development and simulation of this model were informed by a comprehensive review of academic articles, grey literature, relevant websites, and publicly available data sets. The proposed hub and spoke model is expected to expand availability of and access to cell and gene therapy in LMICs and presents a comprehensive framework for the roles of core stakeholders, laying the groundwork for more equitable access to these lifesaving therapies. More research is needed to explore the practical adoption and implications of this model.","PeriodicalId":12699,"journal":{"name":"Gene Therapy","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41434-023-00425-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71411948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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: 0

Implications of maternal-fetal health on perinatal stem cell banking 母婴健康对围产期干细胞库的影响。

IF 5.1 3区医学

Gene Therapy Pub Date : 2023-10-26 DOI: 10.1038/s41434-023-00426-w

Dandan Zhu, Mehri Barabadi, Courtney McDonald, Gina Kusuma, Ishmael Miguel Inocencio, Rebecca Lim

引用次数: 0

Prednisolone and rapamycin reduce the plasma cell gene signature and may improve AAV gene therapy in cynomolgus macaques 泼尼松龙和雷帕霉素降低了食蟹猴的浆细胞基因特征，并可能改善AAV基因治疗。

IF 5.1 3区医学

Gene Therapy Pub Date : 2023-10-13 DOI: 10.1038/s41434-023-00423-z

Alexander Kistner, Jessica A. Chichester, Lili Wang, Roberto Calcedo, Jenny A. Greig, Leah N. Cardwell, Margaret C. Wright, Julien Couthouis, Sunjay Sethi, Brian E. McIntosh, Kathleen McKeever, Samuel Wadsworth, James M. Wilson, Emil Kakkis, Barbara A. Sullivan

{"title":"Prednisolone and rapamycin reduce the plasma cell gene signature and may improve AAV gene therapy in cynomolgus macaques","authors":"Alexander Kistner, Jessica A. Chichester, Lili Wang, Roberto Calcedo, Jenny A. Greig, Leah N. Cardwell, Margaret C. Wright, Julien Couthouis, Sunjay Sethi, Brian E. McIntosh, Kathleen McKeever, Samuel Wadsworth, James M. Wilson, Emil Kakkis, Barbara A. Sullivan","doi":"10.1038/s41434-023-00423-z","DOIUrl":"10.1038/s41434-023-00423-z","url":null,"abstract":"Adeno-associated virus (AAV) vector gene therapy is a promising approach to treat rare genetic diseases; however, an ongoing challenge is how to best modulate host immunity to improve transduction efficiency and therapeutic outcomes. This report presents two studies characterizing multiple prophylactic immunosuppression regimens in male cynomolgus macaques receiving an AAVrh10 gene therapy vector expressing human coagulation factor VIII (hFVIII). In study 1, no immunosuppression was compared with prednisolone, rapamycin (or sirolimus), rapamycin and cyclosporin A in combination, and cyclosporin A and azathioprine in combination. Prednisolone alone demonstrated higher mean peripheral blood hFVIII expression; however, this was not sustained upon taper. Anti-capsid and anti-hFVIII antibody responses were robust, and vector genomes and transgene mRNA levels were similar to no immunosuppression at necropsy. Study 2 compared no immunosuppression with prednisolone alone or in combination with rapamycin or methotrexate. The prednisolone/rapamycin group demonstrated an increase in mean hFVIII expression and a mean delay in anti-capsid IgG development until after rapamycin taper. Additionally, a significant reduction in the plasma cell gene signature was observed with prednisolone/rapamycin, suggesting that rapamycin’s tolerogenic effects may include plasma cell differentiation blockade. Immunosuppression with prednisolone and rapamycin in combination could improve therapeutic outcomes in AAV vector gene therapy.","PeriodicalId":12699,"journal":{"name":"Gene Therapy","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2023-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41434-023-00423-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41198902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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: 0

p53 dry gene powder enhances anti-cancer effects of chemotherapy against malignant pleural mesothelioma p53干基因粉增强化疗对恶性胸膜间皮瘤的抗癌作用。

IF 5.1 3区医学

Gene Therapy Pub Date : 2023-10-13 DOI: 10.1038/s41434-023-00424-y

Naomi Muramatsu, Misa Ichikawa, Tomoko Katagiri, Yumi Taguchi, Takashi Hatanaka, Tomoyuki Okuda, Hirokazu Okamoto

引用次数: 0

Artificial microRNA suppresses C9ORF72 variants and decreases toxic dipeptide repeat proteins in vivo 人工微小RNA在体内抑制C9ORF72变体并降低毒性二肽重复蛋白。

IF 5.1 3区医学

Gene Therapy Pub Date : 2023-09-26 DOI: 10.1038/s41434-023-00418-w

Gabriela Toro Cabrera, Katharina E. Meijboom, Abbas Abdallah, Helene Tran, Zachariah Foster, Alexandra Weiss, Nicholas Wightman, Rachel Stock, Tania Gendron, Alisha Gruntman, Anthony Giampetruzzi, Leonard Petrucelli, Robert H. Brown Jr, Christian Mueller

引用次数: 0

Long-term effects of a fat-directed FGF21 gene therapy in aged female mice 脂肪导向的FGF21基因治疗对老年雌性小鼠的长期影响。

IF 5.1 3区医学

Gene Therapy Pub Date : 2023-09-12 DOI: 10.1038/s41434-023-00422-0

Jacqueline M. Anderson, W. David Arnold, Wei Huang, Alissa Ray, Gregory Owendoff, Lei Cao

{"title":"Long-term effects of a fat-directed FGF21 gene therapy in aged female mice","authors":"Jacqueline M. Anderson, W. David Arnold, Wei Huang, Alissa Ray, Gregory Owendoff, Lei Cao","doi":"10.1038/s41434-023-00422-0","DOIUrl":"10.1038/s41434-023-00422-0","url":null,"abstract":"Fibroblast growth factor 21 (FGF21) has been developed as a potential therapeutic agent for metabolic syndromes. Moreover, FGF21 is considered a pro-longevity hormone because transgenic mice overexpressing FGF21 display extended lifespan, raising the possibility of using FGF21 to promote healthy aging. We recently showed that visceral fat directed FGF21 gene therapy improves metabolic and immune health in insulin resistant BTBR mice. Here, we used a fat directed rAAV-FGF21 vector in 17-month-old female mice to investigate whether long-term FGF21 gene transfer could mitigate aging-related functional decline. Animals with FGF21 treatment displayed a steady, significant lower body weight over 7-month of the study compared to age-matched control mice. FGF21 treatment reduced adiposity and increased relative lean mass and energy expenditure associated with almost 100 folds higher serum level of FGF21. However, those changes were not translated into benefits on muscle function and did not affect metabolic function of liver. Overall, we have demonstrated that a single dose of fat-directed AAV-FGF21 treatment can provide a sustainable, high serum level of FGF21 over long period of time, and mostly influences adipose tissue homeostasis and energy expenditure. High levels of FGF21 alone in aged mice is not sufficient to improve liver or muscle functions.","PeriodicalId":12699,"journal":{"name":"Gene Therapy","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2023-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10224682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Acoustically targeted noninvasive gene therapy in large brain volumes 大容量脑声学靶向非侵入性基因治疗。

IF 5.1 3区医学

Gene Therapy Pub Date : 2023-09-12 DOI: 10.1038/s41434-023-00421-1

Shirin Nouraein, Sangsin Lee, Vidal A. Saenz, Huckie C. Del Mundo, Joycelyn Yiu, Jerzy O. Szablowski

{"title":"Acoustically targeted noninvasive gene therapy in large brain volumes","authors":"Shirin Nouraein, Sangsin Lee, Vidal A. Saenz, Huckie C. Del Mundo, Joycelyn Yiu, Jerzy O. Szablowski","doi":"10.1038/s41434-023-00421-1","DOIUrl":"10.1038/s41434-023-00421-1","url":null,"abstract":"Focused Ultrasound Blood-Brain Barrier Opening (FUS-BBBO) can deliver adeno-associated viral vectors (AAVs) to treat genetic disorders of the brain. However, such disorders often affect large brain regions. Moreover, the applicability of FUS-BBBO in the treatment of brain-wide genetic disorders has not yet been evaluated. Herein, we evaluated the transduction efficiency and safety of opening up to 105 sites simultaneously. Increasing the number of targeted sites increased gene delivery efficiency at each site. We achieved transduction of up to 60% of brain cells with comparable efficiency in the majority of the brain regions. Furthermore, gene delivery with FUS-BBBO was safe even when all 105 sites were targeted simultaneously without negative effects on animal weight or neuronal loss. To evaluate the application of multi-site FUS-BBBO for gene therapy, we used it for gene editing using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system and found effective gene editing, but also a loss of neurons at the targeted sites. Overall, this study provides a brain-wide map of transduction efficiency, shows the synergistic effect of multi-site targeting on transduction efficiency, and is the first example of large brain volume gene editing after noninvasive gene delivery with FUS-BBBO.","PeriodicalId":12699,"journal":{"name":"Gene Therapy","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2023-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10216070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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