CA3005246A1 - Compositions and methods for treatment of central nervous system diseases - Google Patents
Compositions and methods for treatment of central nervous system diseases Download PDFInfo
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- CA3005246A1 CA3005246A1 CA3005246A CA3005246A CA3005246A1 CA 3005246 A1 CA3005246 A1 CA 3005246A1 CA 3005246 A CA3005246 A CA 3005246A CA 3005246 A CA3005246 A CA 3005246A CA 3005246 A1 CA3005246 A1 CA 3005246A1
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| EP3201339A4 (en) | 2014-10-03 | 2018-09-19 | Cold Spring Harbor Laboratory | Targeted augmentation of nuclear gene output |
| EP3359685A1 (en) | 2015-10-09 | 2018-08-15 | University Of Southampton | Modulation of gene expression and screening for deregulated protein expression |
| KR102604132B1 (ko) | 2015-12-14 | 2023-11-17 | 콜드스프링하버러보러토리 | 상염색체 우성 정신 지체 5 및 드라베 증후군의 치료를 위한 안티센스 올리고머 |
| US11096956B2 (en) | 2015-12-14 | 2021-08-24 | Stoke Therapeutics, Inc. | Antisense oligomers and uses thereof |
| CA3005131A1 (en) * | 2015-12-14 | 2017-06-22 | Cold Spring Harbor Laboratory | Antisense oligomers for treatment of tuberous sclerosis complex |
| KR102712656B1 (ko) | 2017-01-23 | 2024-10-04 | 리제너론 파마슈티칼스 인코포레이티드 | Hsd17b13 변종 및 이것의 용도 |
| US11479802B2 (en) | 2017-04-11 | 2022-10-25 | Regeneron Pharmaceuticals, Inc. | Assays for screening activity of modulators of members of the hydroxy steroid (17-beta) dehydrogenase (HSD17B) family |
| SI3673080T1 (sl) | 2017-08-25 | 2024-03-29 | Stoke Therapeutics, Inc. | Protismiselni oligomeri za zdravljenje bolezenskih stanj in bolezni |
| EP3461837A1 (en) * | 2017-09-28 | 2019-04-03 | Secarna Pharmaceuticals GmbH & Co. KG | Inhibitor inhibiting the expression of pprx1 |
| AU2018348195B2 (en) | 2017-10-11 | 2025-05-15 | Regeneron Pharmaceuticals, Inc. | Inhibition of HSD17B13 in the treatment of liver disease in patients expressing the PNPLA3 I148M variation |
| HRP20250322T1 (hr) * | 2017-10-23 | 2025-06-06 | Stoke Therapeutics, Inc. | Protusmisleni oligomeri, namijenjeni liječenju stanja i bolesti uzrokovanih raspadanjem rna posredovanim besmislenim mutacijama |
| BR112020018758A2 (pt) | 2018-03-21 | 2021-01-26 | Regeneron Pharmaceuticals, Inc. | agente de ácido ribonucleico de fita dupla, célula, vetor, composição farmacêutica, e, métodos para inibição da expressão de 17¿-hidroxiesteroide desidrogenases tipo 13, para tratamento de um indivíduo, para prevenção de um sintoma em um indivíduo, para redução do risco de desenvolver doença hepática crônica, para inibição da progressão de esteatose, para inibição do acúmulo de gotículas de lipídios |
| BR112020022512A2 (pt) | 2018-05-04 | 2021-05-04 | Stoke Therapeutics, Inc. | métodos e composições para tratamento de doença de armazenamento de éster de colesteril |
| CA3110211A1 (en) | 2018-08-20 | 2020-02-27 | Rogcon, Inc. | Antisense oligonucleotides targeting scn2a for the treatment of scn1a encephalopathies |
| EP3942049A4 (en) | 2019-03-20 | 2023-10-18 | President And Fellows Of Harvard College | ANTISENSE OLIGONUCLEOTIDE BASED PROGRANULIN AUGMENTATION THERAPY FOR NEURODEGENERATIVE DISEASES |
| US20220228146A1 (en) * | 2019-05-06 | 2022-07-21 | The Children's Hospital Of Philadelphia | Micro-rna site blocking oligonucleotides for the treatment of epileptic encephalopathy and neurodevelopmental disorders |
| JP2022531809A (ja) * | 2019-05-14 | 2022-07-11 | デューク ユニバーシティ | ＡＴＰａｓｅ媒介性疾患の処置のための組成物および方法 |
| US20220333110A1 (en) * | 2019-09-30 | 2022-10-20 | The University Of Tokyo | Nucleic acid that inhibits expression of mex3b gene, mex3b gene expression inhibiting agent, method for inhibiting mex3b gene expression, and prophylactic or therapeutic agent for disease caused by mex3b gene expression |
| JP2023524671A (ja) * | 2020-04-27 | 2023-06-13 | ウニベルジテート ウルム | Ｓｈａｎｋ３の発現を増加させるアンチセンスオリゴヌクレオチド |
| AU2021270720A1 (en) | 2020-05-11 | 2022-12-08 | Stoke Therapeutics, Inc. | OPA1 antisense oligomers for treatment of conditions and diseases |
| US20240392297A1 (en) * | 2020-12-23 | 2024-11-28 | Eli Lilly And Company | Rna therapeutics and methods of use thereof |
| IL307167A (en) * | 2021-04-05 | 2023-11-01 | Itayandbiond Ltd | Small activating RNA that increases expression of SHANK and a method for treating intellectual disabilities and associated diseases associated with SHANK haploinsufficiency |
| CN118434858A (zh) * | 2021-12-07 | 2024-08-02 | 豪夫迈·罗氏有限公司 | 靶向actl6b的反义寡核苷酸 |
| CN118647405A (zh) * | 2022-01-25 | 2024-09-13 | 上海魁特迪生物科技有限公司 | 改善认知障碍的方法 |
| WO2023168427A1 (en) | 2022-03-03 | 2023-09-07 | Yale University | Compositions and methods for delivering therapeutic polynucleotides for exon skipping |
| CN114836532A (zh) * | 2022-04-28 | 2022-08-02 | 福建医科大学附属第一医院 | Eif2b5基因突变作为靶标在诊断消融性白质脑病中的应用 |
| WO2024126654A1 (en) * | 2022-12-14 | 2024-06-20 | F. Hoffmann-La Roche Ag | Antisense oligonucleotides targeting actl6b |
| WO2024226471A2 (en) * | 2023-04-24 | 2024-10-31 | Biomarin Pharmaceutical Inc. | Compositions and methods for treating stxbp1 disorders |
| WO2025038842A1 (en) * | 2023-08-15 | 2025-02-20 | The Children's Medical Center Corporation | Systems and methods for modifying a polynucleotide |
| CN117122688B (zh) * | 2023-08-31 | 2024-06-04 | 中国科学院脑科学与智能技术卓越创新中心 | 作用于前脑兴奋性神经元的prrt2及其上调剂的应用 |
| WO2025217494A1 (en) * | 2024-04-11 | 2025-10-16 | The University Of Chicago | Splice-switching oligonucleotides for treating cacna1a-associated disorders |
| WO2025250031A1 (en) * | 2024-05-31 | 2025-12-04 | Bial - Portela & Ca., S.A. | Antisense oligonucleotides for treatment of stxbp1-related developmental epileptic encephalopathy |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4866042A (en) | 1987-11-18 | 1989-09-12 | Neuwelt Edward A | Method for the delivery of genetic material across the blood brain barrier |
| US6294520B1 (en) | 1989-03-27 | 2001-09-25 | Albert T. Naito | Material for passage through the blood-brain barrier |
| US5151510A (en) | 1990-04-20 | 1992-09-29 | Applied Biosystems, Inc. | Method of synethesizing sulfurized oligonucleotide analogs |
| FI951404A7 (fi) | 1992-09-25 | 1995-03-24 | Rhone Poulenc Rorer Sa | Adenovirusvektoreita vieraiden geenien siirtämiseksi keskushermostojärjestelmän , erityisesti aivojen, soluihin |
| US5656612A (en) | 1994-05-31 | 1997-08-12 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotide modulation of raf gene expression |
| FR2727867B1 (fr) | 1994-12-13 | 1997-01-31 | Rhone Poulenc Rorer Sa | Transfert de genes dans les motoneurones medullaires au moyen de vecteurs adenoviraux |
| US6936589B2 (en) | 2001-09-28 | 2005-08-30 | Albert T. Naito | Parenteral delivery systems |
| WO2007047913A2 (en) | 2005-10-20 | 2007-04-26 | Isis Pharmaceuticals, Inc | Compositions and methods for modulation of lmna expression |
| EP3705125B1 (en) | 2007-12-04 | 2023-07-05 | Alnylam Pharmaceuticals, Inc. | Carbohydrate conjugates as delivery agents for oligonucleotides |
| JP5608863B2 (ja) * | 2007-12-28 | 2014-10-15 | 公立大学法人横浜市立大学 | 新生児期〜乳児期発症の難治性てんかんの検出方法 |
| SI3449926T1 (sl) | 2009-06-17 | 2020-04-30 | Biogen Ma Inc. | Sestave in metode za modulacijo združevanja SMN2 pri subjektu |
| US20140128449A1 (en) | 2011-04-07 | 2014-05-08 | The Board Of Regents Of The University Of Texas System | Oligonucleotide modulation of splicing |
| WO2012178122A2 (en) * | 2011-06-23 | 2012-12-27 | Cold Spring Harbor Laboratory | Phenocopy model of disease |
| EP3248982A1 (en) | 2011-07-19 | 2017-11-29 | Wave Life Sciences Ltd. | Thiosulfonate reagents for the synthesis of functionalized nucleic acids |
| CA2930859C (en) | 2013-09-04 | 2022-05-03 | Cold Spring Harbor Laboratory | Reducing nonsense-mediated mrna decay |
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| JP7049249B2 (ja) | 2022-04-06 |
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| EP4104867A3 (en) | 2023-03-01 |
| EP3389725A1 (en) | 2018-10-24 |
| EP3389725B1 (en) | 2022-04-06 |
| WO2017106382A1 (en) | 2017-06-22 |
| JP2022062141A (ja) | 2022-04-19 |
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