Open-label, single dose clinical trial of scAAV9.U7.ACCA via peripheral limb vein injection for Duchenne muscular dystrophy boys who have a duplication of exon 2.

开始日期2020-01-15

申办/合作机构

Nationwide Children's Hospital

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100 项与 scAAV9.U7.ACCA 相关的临床结果

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100 项与 scAAV9.U7.ACCA 相关的转化医学

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100 项与 scAAV9.U7.ACCA 相关的专利（医药）

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项与 scAAV9.U7.ACCA 相关的文献（医药）

2023-12-01·Molecular Therapy - Methods & Clinical Development

Persistence of exon 2 skipping and dystrophin expression at 18 months after U7snRNA-mediated therapy in the Dup2 mouse model

Article

作者: Lay, Jacob W ; Vetter, Tatyana A ; Rohan, Natalie L ; Bradley, Adrienne J ; Gushchina, Liubov V ; Flanigan, Kevin M ; Wein, Nicolas ; Frair, Emma C

Duchenne muscular dystrophy (DMD) is a progressive X-linked disease caused by mutations in the DMD gene that prevent the expression of a functional dystrophin protein. Exon duplications represent 6%-11% of mutations, and duplications of exon 2 (Dup2) are the most common (∼11%) of duplication mutations. An exon-skipping strategy for Dup2 mutations presents a large therapeutic window. Skipping one exon copy results in full-length dystrophin expression, whereas skipping of both copies (Del2) activates an internal ribosomal entry site (IRES) in exon 5, inducing the expression of a highly functional truncated dystrophin isoform. We have previously confirmed the therapeutic efficacy of AAV9.U7snRNA-mediated skipping in the Dup2 mouse model and showed the absence of off-target splicing effects and lack of toxicity in mice and nonhuman primates. Here, we report long-term dystrophin expression data following the treatment of 3-month-old Dup2 mice with the scAAV9.U7.ACCA vector. Significant exon 2 skipping and robust dystrophin expression in the muscles and hearts of treated mice persist at 18 months after treatment, along with the partial rescue of muscle function. These data extend our previous findings and show that scAAV9.U7.ACCA provides long-term protection by restoring the disrupted dystrophin reading frame in the context of exon 2 duplications.

100 项与 scAAV9.U7.ACCA 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
杜氏肌营养不良症	临床2期	-	Astellas Gene Therapies, Inc.	-

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


scAAV9.U7-ACCA (ASGCT2023)	N/A	杜氏肌营养不良症	3	scAAV9.U7-ACCA	鑰鹽膚鹽築艱鹽鑰夢範(鏇鏇願範範築製構繭鬱) = 壓醖遞鹹艱遞蓋鏇鹹觸蓋構願淵製齋醖鬱繭繭 (蓋襯鹽簾鬱艱餘醖鏇積 ) 更多	积极	2023-05-01
ASGCT2022	N/A	杜氏肌营养不良症 exon 2 duplications	3	scAAV9.U7-ACCA	鹽鹹醖齋觸蓋遞蓋鏇範(顧鬱廠顧夢壓構襯繭糧) = 醖積餘築壓簾範範選餘鹽簾窪衊襯醖襯膚鹹製 (憲廠遞築壓鏇鏇蓋願繭 ) 更多	积极	2022-05-02
NCT04240314 (ASGCT2021)	临床1/2期	杜氏肌营养不良症	2	scAAV9.U7-ACCA vector	願齋範鏇窪繭簾鑰製範(願觸製齋願膚憲壓遞蓋) = subtle improvements were seen in the 100 meter timed test for subject 1 (54.3% predicted to 58.8% predicted) at 6 months and 61.4% predicted at 12 months 選夢淵鏇鑰夢襯憲膚簾 (壓艱範網憲艱鹽淵願齋 ) 更多	积极	2021-04-27