可能完成的任务遗传代谢疾病的基因疗法。

IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Journal of Inherited Metabolic Disease Pub Date : 2024-01-14 DOI:10.1002/jimd.12708
Julien Baruteau, Nandaki Keshavan, Charles P. Venditti
{"title":"可能完成的任务遗传代谢疾病的基因疗法。","authors":"Julien Baruteau,&nbsp;Nandaki Keshavan,&nbsp;Charles P. Venditti","doi":"10.1002/jimd.12708","DOIUrl":null,"url":null,"abstract":"<p>Since the description of ‘inborn errors of metabolism’ as a novel field of medicine by Archibald Garrod in 1908,<span><sup>1</sup></span> various breakthroughs in management and therapeutic milestones have been achieved: specific diets, newborn screening and enzyme replacement therapy to name a few (Figure 1). Genomic assays, including exome, genome and RNA sequencing, have led to the identification of a rapidly growing number of new inborn errors of metabolism and many new patients in recent years.</p><p>Gene therapy centred around gene addition and editing therapy has emerged in parallel with the technological progress in engineering nucleic acids, nucleases and viruses. Seminal early milestones have raised a huge hope for inherited metabolic diseases (IMDs) with little or no therapeutic benefit under standard of care.<span><sup>2, 3</sup></span> Complex biotechnologies such as gene addition mediated by adeno-associated viral vectors (AAV) and integrating vectors that rely upon lentiviral and CRISPR-Cas9 mediated gene-editing platforms are now the basis of approved drug products for monogenic diseases.<span><sup>4-6</sup></span> Application of gene therapy has been studied in many rare IMDs. Proof-of-concept data using varied technologies, nucleic acids, and delivery platforms to achieve gene replacement, integration and editing, especially in the liver and the central nervous system, have served to enable a wide range of exciting new therapies for genetic and metabolic disorders. Whilst first-in-man clinical trials expand, the challenges for this rapidly evolving field include the development of safer and more efficient vectors, more accessible technologies, and the development of new regulatory paradigms to expedite approvals. Today, a one-size-fits-all strategy remains elusive for most disorders given that even within a rare IEM patient population, phenotypic heterogeneity, variable disease progression and uncertainties surrounding the natural history can further complicate the risk–benefit balance for clinical trials.</p><p>This themed issue of <i>Journal of Inherited Metabolic Disease</i> reviews state-of-the-art of gene therapy technologies applied to various inborn metabolic diseases. It provides updates on clinical successes, limitations and future directions whilst considering specificities for liver and fetal applications. The special issue starts with two reviews concerning liver-directed gene therapy. Baruteau et al. present an overview of the progress, challenges and perspectives for the main liver IMDs from a clinical perspective.<span><sup>7</sup></span> Chuecos and Lagor introduce AAV, which represent currently the leading liver-targeting gene therapy technology, with a particular focus on AAV physiology, AAV transduction including sex differences and an updated review of AAV clinical trials for liver IMDs and their contribution to the field of gene therapy.<span><sup>8</sup></span> Pontoizeau et al. provide an additional proof of concept of neonatal gene therapy for maple syrup urine disease.<span><sup>9</sup></span> Duff et al. review the specificities, development and perspectives of gene therapy for urea cycle defects.<span><sup>10</sup></span> Chandler and Venditti summarise the preclinical studies and clinical trials of genetic therapies developed for methylmalonic and propionic acidaemias and lessons learned over the years.<span><sup>11</sup></span> Martinez et al. provide an update on proof of concept in animal models and clinical trials of gene therapy for phenylketonuria, including recent innovative preclinical approaches of introducing an acquired competitive advantage of genetically modified hepatocytes.<span><sup>12</sup></span> Koeberl et al. review gene therapy advances for glycogen storage diseases (GSDs) from preclinical to clinical studies, with a particular focus on GSDI, II and III.<span><sup>13</sup></span> Sellier et al. report a muscle-specific, liver-detargeted AAV gene therapy to treat a neonatal and adult Pompe mouse model.<span><sup>14</sup></span> Rossi and Brunetti-Pierri review the development of ex vivo and in vivo gene therapy approaches for mucopolysaccharidosis (MPS) with detailed sections for MPSI, MPSII, MPSIII, MPSIV and MPSVI.<span><sup>15</sup></span> Keshavan et al. provide a perspective on the development of gene therapy for primary mitochondrial diseases.<span><sup>16</sup></span> Ng et al. show the epic journey to develop gene therapy approaches for inherited neurotransmitter defects culminating with the recent approval of eladocagene exuparvovec (Upstaza™) for aromatic L-amino acid decarboxylase (AADC) deficiency in late 2022.<span><sup>17</sup></span> To conclude this special issue, Waddington et al. present a magistral review of fetal gene therapy and its complex implications from preclinical evidence to translation, safety and ethics for both the fetus and the mother.<span><sup>18</sup></span></p><p>In conclusion, numerous proof-of-concept studies have investigated different gene therapy technologies in preclinical models of IMDs. The wider translation of these promising therapeutic strategies to patients, and overcoming their inherent limitations, remains the bottleneck. Supported by improved knowledge gathered from numerous ongoing clinical trials for inborn errors of metabolism, the translation of innovative gene therapy for rare diseases, which remains a long and arduous journey, is gradually reaching patients, and is uplifted by the hope of a brighter outcome and a much-improved quality of life.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"47 1","pages":"5-6"},"PeriodicalIF":4.2000,"publicationDate":"2024-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.12708","citationCount":"0","resultStr":"{\"title\":\"Mission possible: Gene therapy for inherited metabolic diseases\",\"authors\":\"Julien Baruteau,&nbsp;Nandaki Keshavan,&nbsp;Charles P. Venditti\",\"doi\":\"10.1002/jimd.12708\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Since the description of ‘inborn errors of metabolism’ as a novel field of medicine by Archibald Garrod in 1908,<span><sup>1</sup></span> various breakthroughs in management and therapeutic milestones have been achieved: specific diets, newborn screening and enzyme replacement therapy to name a few (Figure 1). Genomic assays, including exome, genome and RNA sequencing, have led to the identification of a rapidly growing number of new inborn errors of metabolism and many new patients in recent years.</p><p>Gene therapy centred around gene addition and editing therapy has emerged in parallel with the technological progress in engineering nucleic acids, nucleases and viruses. Seminal early milestones have raised a huge hope for inherited metabolic diseases (IMDs) with little or no therapeutic benefit under standard of care.<span><sup>2, 3</sup></span> Complex biotechnologies such as gene addition mediated by adeno-associated viral vectors (AAV) and integrating vectors that rely upon lentiviral and CRISPR-Cas9 mediated gene-editing platforms are now the basis of approved drug products for monogenic diseases.<span><sup>4-6</sup></span> Application of gene therapy has been studied in many rare IMDs. Proof-of-concept data using varied technologies, nucleic acids, and delivery platforms to achieve gene replacement, integration and editing, especially in the liver and the central nervous system, have served to enable a wide range of exciting new therapies for genetic and metabolic disorders. Whilst first-in-man clinical trials expand, the challenges for this rapidly evolving field include the development of safer and more efficient vectors, more accessible technologies, and the development of new regulatory paradigms to expedite approvals. Today, a one-size-fits-all strategy remains elusive for most disorders given that even within a rare IEM patient population, phenotypic heterogeneity, variable disease progression and uncertainties surrounding the natural history can further complicate the risk–benefit balance for clinical trials.</p><p>This themed issue of <i>Journal of Inherited Metabolic Disease</i> reviews state-of-the-art of gene therapy technologies applied to various inborn metabolic diseases. It provides updates on clinical successes, limitations and future directions whilst considering specificities for liver and fetal applications. The special issue starts with two reviews concerning liver-directed gene therapy. Baruteau et al. present an overview of the progress, challenges and perspectives for the main liver IMDs from a clinical perspective.<span><sup>7</sup></span> Chuecos and Lagor introduce AAV, which represent currently the leading liver-targeting gene therapy technology, with a particular focus on AAV physiology, AAV transduction including sex differences and an updated review of AAV clinical trials for liver IMDs and their contribution to the field of gene therapy.<span><sup>8</sup></span> Pontoizeau et al. provide an additional proof of concept of neonatal gene therapy for maple syrup urine disease.<span><sup>9</sup></span> Duff et al. review the specificities, development and perspectives of gene therapy for urea cycle defects.<span><sup>10</sup></span> Chandler and Venditti summarise the preclinical studies and clinical trials of genetic therapies developed for methylmalonic and propionic acidaemias and lessons learned over the years.<span><sup>11</sup></span> Martinez et al. provide an update on proof of concept in animal models and clinical trials of gene therapy for phenylketonuria, including recent innovative preclinical approaches of introducing an acquired competitive advantage of genetically modified hepatocytes.<span><sup>12</sup></span> Koeberl et al. review gene therapy advances for glycogen storage diseases (GSDs) from preclinical to clinical studies, with a particular focus on GSDI, II and III.<span><sup>13</sup></span> Sellier et al. report a muscle-specific, liver-detargeted AAV gene therapy to treat a neonatal and adult Pompe mouse model.<span><sup>14</sup></span> Rossi and Brunetti-Pierri review the development of ex vivo and in vivo gene therapy approaches for mucopolysaccharidosis (MPS) with detailed sections for MPSI, MPSII, MPSIII, MPSIV and MPSVI.<span><sup>15</sup></span> Keshavan et al. provide a perspective on the development of gene therapy for primary mitochondrial diseases.<span><sup>16</sup></span> Ng et al. show the epic journey to develop gene therapy approaches for inherited neurotransmitter defects culminating with the recent approval of eladocagene exuparvovec (Upstaza™) for aromatic L-amino acid decarboxylase (AADC) deficiency in late 2022.<span><sup>17</sup></span> To conclude this special issue, Waddington et al. present a magistral review of fetal gene therapy and its complex implications from preclinical evidence to translation, safety and ethics for both the fetus and the mother.<span><sup>18</sup></span></p><p>In conclusion, numerous proof-of-concept studies have investigated different gene therapy technologies in preclinical models of IMDs. The wider translation of these promising therapeutic strategies to patients, and overcoming their inherent limitations, remains the bottleneck. Supported by improved knowledge gathered from numerous ongoing clinical trials for inborn errors of metabolism, the translation of innovative gene therapy for rare diseases, which remains a long and arduous journey, is gradually reaching patients, and is uplifted by the hope of a brighter outcome and a much-improved quality of life.</p>\",\"PeriodicalId\":16281,\"journal\":{\"name\":\"Journal of Inherited Metabolic Disease\",\"volume\":\"47 1\",\"pages\":\"5-6\"},\"PeriodicalIF\":4.2000,\"publicationDate\":\"2024-01-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.12708\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Inherited Metabolic Disease\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/jimd.12708\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Inherited Metabolic Disease","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jimd.12708","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0

摘要

从众多正在进行的先天性代谢错误临床试验中收集到的更多知识支持着罕见病创新基因疗法的转化(这仍然是一个漫长而艰巨的旅程),它正逐渐惠及患者,并因患者对更光明的结果和更高的生活质量的希望而振奋。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

摘要图片

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Mission possible: Gene therapy for inherited metabolic diseases

Since the description of ‘inborn errors of metabolism’ as a novel field of medicine by Archibald Garrod in 1908,1 various breakthroughs in management and therapeutic milestones have been achieved: specific diets, newborn screening and enzyme replacement therapy to name a few (Figure 1). Genomic assays, including exome, genome and RNA sequencing, have led to the identification of a rapidly growing number of new inborn errors of metabolism and many new patients in recent years.

Gene therapy centred around gene addition and editing therapy has emerged in parallel with the technological progress in engineering nucleic acids, nucleases and viruses. Seminal early milestones have raised a huge hope for inherited metabolic diseases (IMDs) with little or no therapeutic benefit under standard of care.2, 3 Complex biotechnologies such as gene addition mediated by adeno-associated viral vectors (AAV) and integrating vectors that rely upon lentiviral and CRISPR-Cas9 mediated gene-editing platforms are now the basis of approved drug products for monogenic diseases.4-6 Application of gene therapy has been studied in many rare IMDs. Proof-of-concept data using varied technologies, nucleic acids, and delivery platforms to achieve gene replacement, integration and editing, especially in the liver and the central nervous system, have served to enable a wide range of exciting new therapies for genetic and metabolic disorders. Whilst first-in-man clinical trials expand, the challenges for this rapidly evolving field include the development of safer and more efficient vectors, more accessible technologies, and the development of new regulatory paradigms to expedite approvals. Today, a one-size-fits-all strategy remains elusive for most disorders given that even within a rare IEM patient population, phenotypic heterogeneity, variable disease progression and uncertainties surrounding the natural history can further complicate the risk–benefit balance for clinical trials.

This themed issue of Journal of Inherited Metabolic Disease reviews state-of-the-art of gene therapy technologies applied to various inborn metabolic diseases. It provides updates on clinical successes, limitations and future directions whilst considering specificities for liver and fetal applications. The special issue starts with two reviews concerning liver-directed gene therapy. Baruteau et al. present an overview of the progress, challenges and perspectives for the main liver IMDs from a clinical perspective.7 Chuecos and Lagor introduce AAV, which represent currently the leading liver-targeting gene therapy technology, with a particular focus on AAV physiology, AAV transduction including sex differences and an updated review of AAV clinical trials for liver IMDs and their contribution to the field of gene therapy.8 Pontoizeau et al. provide an additional proof of concept of neonatal gene therapy for maple syrup urine disease.9 Duff et al. review the specificities, development and perspectives of gene therapy for urea cycle defects.10 Chandler and Venditti summarise the preclinical studies and clinical trials of genetic therapies developed for methylmalonic and propionic acidaemias and lessons learned over the years.11 Martinez et al. provide an update on proof of concept in animal models and clinical trials of gene therapy for phenylketonuria, including recent innovative preclinical approaches of introducing an acquired competitive advantage of genetically modified hepatocytes.12 Koeberl et al. review gene therapy advances for glycogen storage diseases (GSDs) from preclinical to clinical studies, with a particular focus on GSDI, II and III.13 Sellier et al. report a muscle-specific, liver-detargeted AAV gene therapy to treat a neonatal and adult Pompe mouse model.14 Rossi and Brunetti-Pierri review the development of ex vivo and in vivo gene therapy approaches for mucopolysaccharidosis (MPS) with detailed sections for MPSI, MPSII, MPSIII, MPSIV and MPSVI.15 Keshavan et al. provide a perspective on the development of gene therapy for primary mitochondrial diseases.16 Ng et al. show the epic journey to develop gene therapy approaches for inherited neurotransmitter defects culminating with the recent approval of eladocagene exuparvovec (Upstaza™) for aromatic L-amino acid decarboxylase (AADC) deficiency in late 2022.17 To conclude this special issue, Waddington et al. present a magistral review of fetal gene therapy and its complex implications from preclinical evidence to translation, safety and ethics for both the fetus and the mother.18

In conclusion, numerous proof-of-concept studies have investigated different gene therapy technologies in preclinical models of IMDs. The wider translation of these promising therapeutic strategies to patients, and overcoming their inherent limitations, remains the bottleneck. Supported by improved knowledge gathered from numerous ongoing clinical trials for inborn errors of metabolism, the translation of innovative gene therapy for rare diseases, which remains a long and arduous journey, is gradually reaching patients, and is uplifted by the hope of a brighter outcome and a much-improved quality of life.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Journal of Inherited Metabolic Disease
Journal of Inherited Metabolic Disease 医学-内分泌学与代谢
CiteScore
9.50
自引率
7.10%
发文量
117
审稿时长
4-8 weeks
期刊介绍: The Journal of Inherited Metabolic Disease (JIMD) is the official journal of the Society for the Study of Inborn Errors of Metabolism (SSIEM). By enhancing communication between workers in the field throughout the world, the JIMD aims to improve the management and understanding of inherited metabolic disorders. It publishes results of original research and new or important observations pertaining to any aspect of inherited metabolic disease in humans and higher animals. This includes clinical (medical, dental and veterinary), biochemical, genetic (including cytogenetic, molecular and population genetic), experimental (including cell biological), methodological, theoretical, epidemiological, ethical and counselling aspects. The JIMD also reviews important new developments or controversial issues relating to metabolic disorders and publishes reviews and short reports arising from the Society''s annual symposia. A distinction is made between peer-reviewed scientific material that is selected because of its significance for other professionals in the field and non-peer- reviewed material that aims to be important, controversial, interesting or entertaining (“Extras”).
期刊最新文献
Issue Information Potential therapeutic uses of L-citrulline beyond genetic urea cycle disorders Epidemiology and economic burden of Wilson disease in France: A nationwide population-based study. Human glyoxylate metabolism revisited: New insights pointing to multi-organ involvement with implications for siRNA-based therapies in primary hyperoxaluria. My path to citrin deficiency.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1