The Dilemma of Choice for Duchenne Patients Eligible for Exon 51 Skipping The European Experience
Antisense oligonucleotide (ASO) mediated exon skipping aims to reframe dystrophin transcripts for patients with Duchenne muscular dystrophy (DMD). Currently 4 ASOs have been approved by the Food and Drug Administration targeting exon 45, 51 and 53 based on low level dystrophin restoration. Additiona...
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| Veröffentlicht in: | Journal of neuromuscular diseases 2023-01, Vol.10 (3), p.315-325 |
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| creator | Aartsma-Rus, Annemieke De Waele, Liesbeth Houwen-Opstal, Saskia Kirschner, Janbernd Krom, Yvonne D. Mercuri, Eugenio Niks, Erik H. Straub, Volker van Duyvenvoorde, Hermine A. Vroom, Elizabeth |
| description | Antisense oligonucleotide (ASO) mediated exon skipping aims to reframe dystrophin transcripts for patients with Duchenne muscular dystrophy (DMD). Currently 4 ASOs have been approved by the Food and Drug Administration targeting exon 45, 51 and 53 based on low level dystrophin restoration. Additional studies to confirm functional effects are ongoing. Furthermore, efforts are ongoing to increase muscle specific delivery of ASOs. Consequently, there are 5 clinical trials ongoing or planned for exon 51 skipping ASOs in Europe. While exon 51 skipping applies to the largest group of patients, DMD expert centers do not have sufficient numbers of patients or capacity to run all these trials in parallel. Even at a national level numbers may be too scarce. At the same time, some families now face the choice between participation in different clinical trials of exon 51 skipping, sometimes in addition to the choice of participating in a micro-dystrophin gene therapy trial. In this opinion paper, we outline the challenges, compare the different exon 51 skipping trials, and outline how different European centers and countries try to cope with running multiple trials in parallel for a small group of eligible patients. |
| doi_str_mv | 10.3233/JND-221648 |
| format | Article |
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Currently 4 ASOs have been approved by the Food and Drug Administration targeting exon 45, 51 and 53 based on low level dystrophin restoration. Additional studies to confirm functional effects are ongoing. Furthermore, efforts are ongoing to increase muscle specific delivery of ASOs. Consequently, there are 5 clinical trials ongoing or planned for exon 51 skipping ASOs in Europe. While exon 51 skipping applies to the largest group of patients, DMD expert centers do not have sufficient numbers of patients or capacity to run all these trials in parallel. Even at a national level numbers may be too scarce. At the same time, some families now face the choice between participation in different clinical trials of exon 51 skipping, sometimes in addition to the choice of participating in a micro-dystrophin gene therapy trial. In this opinion paper, we outline the challenges, compare the different exon 51 skipping trials, and outline how different European centers and countries try to cope with running multiple trials in parallel for a small group of eligible patients.</description><identifier>ISSN: 2214-3599</identifier><identifier>EISSN: 2214-3602</identifier><identifier>DOI: 10.3233/JND-221648</identifier><identifier>PMID: 36911945</identifier><language>eng</language><publisher>London, England: SAGE Publications</publisher><subject>Antisense oligonucleotides ; Antisense therapy ; Clinical trials ; Duchenne's muscular dystrophy ; Dystrophin ; Dystrophin - genetics ; Exon skipping ; Exons ; Gene therapy ; Humans ; Muscular Dystrophy, Duchenne - drug therapy ; Muscular Dystrophy, Duchenne - therapy ; Oligonucleotides ; Oligonucleotides, Antisense - therapeutic use</subject><ispartof>Journal of neuromuscular diseases, 2023-01, Vol.10 (3), p.315-325</ispartof><rights>2023 – The authors. Published by IOS Press</rights><rights>Copyright IOS Press BV 2023</rights><rights>2023 – The authors. Published by IOS Press 2023</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c439t-920fb961ed524d0fe81d7472860a019a96b455d09128ebaa38a2a7bb60a3ab233</citedby><cites>FETCH-LOGICAL-c439t-920fb961ed524d0fe81d7472860a019a96b455d09128ebaa38a2a7bb60a3ab233</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.3233/JND-221648$$EPDF$$P50$$Gsage$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.3233/JND-221648$$EHTML$$P50$$Gsage$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,21966,27853,27924,27925,44945,45333</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36911945$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Aartsma-Rus, Annemieke</creatorcontrib><creatorcontrib>De Waele, Liesbeth</creatorcontrib><creatorcontrib>Houwen-Opstal, Saskia</creatorcontrib><creatorcontrib>Kirschner, Janbernd</creatorcontrib><creatorcontrib>Krom, Yvonne D.</creatorcontrib><creatorcontrib>Mercuri, Eugenio</creatorcontrib><creatorcontrib>Niks, Erik H.</creatorcontrib><creatorcontrib>Straub, Volker</creatorcontrib><creatorcontrib>van Duyvenvoorde, Hermine A.</creatorcontrib><creatorcontrib>Vroom, Elizabeth</creatorcontrib><title>The Dilemma of Choice for Duchenne Patients Eligible for Exon 51 Skipping The European Experience</title><title>Journal of neuromuscular diseases</title><addtitle>J Neuromuscul Dis</addtitle><description>Antisense oligonucleotide (ASO) mediated exon skipping aims to reframe dystrophin transcripts for patients with Duchenne muscular dystrophy (DMD). Currently 4 ASOs have been approved by the Food and Drug Administration targeting exon 45, 51 and 53 based on low level dystrophin restoration. Additional studies to confirm functional effects are ongoing. Furthermore, efforts are ongoing to increase muscle specific delivery of ASOs. Consequently, there are 5 clinical trials ongoing or planned for exon 51 skipping ASOs in Europe. While exon 51 skipping applies to the largest group of patients, DMD expert centers do not have sufficient numbers of patients or capacity to run all these trials in parallel. Even at a national level numbers may be too scarce. At the same time, some families now face the choice between participation in different clinical trials of exon 51 skipping, sometimes in addition to the choice of participating in a micro-dystrophin gene therapy trial. In this opinion paper, we outline the challenges, compare the different exon 51 skipping trials, and outline how different European centers and countries try to cope with running multiple trials in parallel for a small group of eligible patients.</description><subject>Antisense oligonucleotides</subject><subject>Antisense therapy</subject><subject>Clinical trials</subject><subject>Duchenne's muscular dystrophy</subject><subject>Dystrophin</subject><subject>Dystrophin - genetics</subject><subject>Exon skipping</subject><subject>Exons</subject><subject>Gene therapy</subject><subject>Humans</subject><subject>Muscular Dystrophy, Duchenne - drug therapy</subject><subject>Muscular Dystrophy, Duchenne - therapy</subject><subject>Oligonucleotides</subject><subject>Oligonucleotides, Antisense - therapeutic use</subject><issn>2214-3599</issn><issn>2214-3602</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>AFRWT</sourceid><sourceid>EIF</sourceid><recordid>eNptkc1u1DAUhS1ERavSDQ-ALLEAIYX6L4m9QmhmClQVIFHW1k1yM-OS2MGeIPr2uEpboGLlK53Px8f3EPKMszdSSHl6_mldCMErpR-RozyoQlZMPL6bS2MOyUlKV4wxXmtZMvOEHMrKcG5UeUTgcod07QYcR6Chp6tdcC3SPkS6ntsdeo_0C-wd-n2im8FtXTMs8uZX8LTk9Ot3N03Ob-mN02aOYULwWZ0w5lstPiUHPQwJT27PY_LtbHO5-lBcfH7_cfXuomiVNPvCCNY3puLYlUJ1rEfNu1rVQlcMGDdgqkaVZccMFxobAKlBQN00WZbQ5E0ck7eL7zQ3I3ZtThxhsFN0I8RrG8DZfxXvdnYbflrORN6NNtnh1a1DDD9mTHs7utTiMIDHMCcral2VXFU1z-iLB-hVmKPP_7NCMy15xlSmXi9UG0NKEfv7NJzZm_Zsbs8u7WX4-d_579G7rjLwcgESbPHPe_-x-g168J9e</recordid><startdate>20230101</startdate><enddate>20230101</enddate><creator>Aartsma-Rus, Annemieke</creator><creator>De Waele, Liesbeth</creator><creator>Houwen-Opstal, Saskia</creator><creator>Kirschner, Janbernd</creator><creator>Krom, Yvonne D.</creator><creator>Mercuri, Eugenio</creator><creator>Niks, Erik H.</creator><creator>Straub, Volker</creator><creator>van Duyvenvoorde, Hermine A.</creator><creator>Vroom, Elizabeth</creator><general>SAGE Publications</general><general>IOS Press BV</general><general>IOS Press</general><scope>AFRWT</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20230101</creationdate><title>The Dilemma of Choice for Duchenne Patients Eligible for Exon 51 Skipping The European Experience</title><author>Aartsma-Rus, Annemieke ; De Waele, Liesbeth ; Houwen-Opstal, Saskia ; Kirschner, Janbernd ; Krom, Yvonne D. ; Mercuri, Eugenio ; Niks, Erik H. ; Straub, Volker ; van Duyvenvoorde, Hermine A. ; Vroom, Elizabeth</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c439t-920fb961ed524d0fe81d7472860a019a96b455d09128ebaa38a2a7bb60a3ab233</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Antisense oligonucleotides</topic><topic>Antisense therapy</topic><topic>Clinical trials</topic><topic>Duchenne's muscular dystrophy</topic><topic>Dystrophin</topic><topic>Dystrophin - genetics</topic><topic>Exon skipping</topic><topic>Exons</topic><topic>Gene therapy</topic><topic>Humans</topic><topic>Muscular Dystrophy, Duchenne - drug therapy</topic><topic>Muscular Dystrophy, Duchenne - therapy</topic><topic>Oligonucleotides</topic><topic>Oligonucleotides, Antisense - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Aartsma-Rus, Annemieke</creatorcontrib><creatorcontrib>De Waele, Liesbeth</creatorcontrib><creatorcontrib>Houwen-Opstal, Saskia</creatorcontrib><creatorcontrib>Kirschner, Janbernd</creatorcontrib><creatorcontrib>Krom, Yvonne D.</creatorcontrib><creatorcontrib>Mercuri, Eugenio</creatorcontrib><creatorcontrib>Niks, Erik H.</creatorcontrib><creatorcontrib>Straub, Volker</creatorcontrib><creatorcontrib>van Duyvenvoorde, Hermine A.</creatorcontrib><creatorcontrib>Vroom, Elizabeth</creatorcontrib><collection>Sage Journals GOLD Open Access 2024</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of neuromuscular diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Aartsma-Rus, Annemieke</au><au>De Waele, Liesbeth</au><au>Houwen-Opstal, Saskia</au><au>Kirschner, Janbernd</au><au>Krom, Yvonne D.</au><au>Mercuri, Eugenio</au><au>Niks, Erik H.</au><au>Straub, Volker</au><au>van Duyvenvoorde, Hermine A.</au><au>Vroom, Elizabeth</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Dilemma of Choice for Duchenne Patients Eligible for Exon 51 Skipping The European Experience</atitle><jtitle>Journal of neuromuscular diseases</jtitle><addtitle>J Neuromuscul Dis</addtitle><date>2023-01-01</date><risdate>2023</risdate><volume>10</volume><issue>3</issue><spage>315</spage><epage>325</epage><pages>315-325</pages><issn>2214-3599</issn><eissn>2214-3602</eissn><abstract>Antisense oligonucleotide (ASO) mediated exon skipping aims to reframe dystrophin transcripts for patients with Duchenne muscular dystrophy (DMD). Currently 4 ASOs have been approved by the Food and Drug Administration targeting exon 45, 51 and 53 based on low level dystrophin restoration. Additional studies to confirm functional effects are ongoing. Furthermore, efforts are ongoing to increase muscle specific delivery of ASOs. Consequently, there are 5 clinical trials ongoing or planned for exon 51 skipping ASOs in Europe. While exon 51 skipping applies to the largest group of patients, DMD expert centers do not have sufficient numbers of patients or capacity to run all these trials in parallel. Even at a national level numbers may be too scarce. At the same time, some families now face the choice between participation in different clinical trials of exon 51 skipping, sometimes in addition to the choice of participating in a micro-dystrophin gene therapy trial. 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| source | Sage IOS Press Publications; MEDLINE; Sage Journals GOLD Open Access 2024 |
| subjects | Antisense oligonucleotides Antisense therapy Clinical trials Duchenne's muscular dystrophy Dystrophin Dystrophin - genetics Exon skipping Exons Gene therapy Humans Muscular Dystrophy, Duchenne - drug therapy Muscular Dystrophy, Duchenne - therapy Oligonucleotides Oligonucleotides, Antisense - therapeutic use |
| title | The Dilemma of Choice for Duchenne Patients Eligible for Exon 51 Skipping The European Experience |
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