文献

J-GLOBAL ID：202202284115451517   整理番号：22A0660110

遺伝子治療:テイ・サックス病に対するAAV遺伝子治療

AAV gene therapy for Tay-Sachs disease

著者 (41件)： FLOTTE Terence R. (Dep. of Pediatrics, UMass Chan Medical School, Worcester, MA, USA) ,  CATALTEPE Oguz (Dep. of Pediatrics, UMass Chan Medical School, Worcester, MA, USA) ,  GERNOUX Gwladys (Dep. of Pediatrics, UMass Chan Medical School, Worcester, MA, USA) ,  BLACKWOOD Meghan (Dep. of Pediatrics, UMass Chan Medical School, Worcester, MA, USA) ,  MUELLER Christian (Dep. of Pediatrics, UMass Chan Medical School, Worcester, MA, USA) ,  BATEMAN Scot (Dep. of Pediatrics, UMass Chan Medical School, Worcester, MA, USA) ,  KEELER Allison M. (Dep. of Pediatrics, UMass Chan Medical School, Worcester, MA, USA) ,  GIBSON Laura (Dep. of Pediatrics, UMass Chan Medical School, Worcester, MA, USA) ,  FLOTTE Terence R. (Horae Gene Therapy Center and The Li Weibo Inst. for Rare Diseases Res., UMass Chan Medical School, Worcester, MA, USA) ,  BATISTA Ana Rita (Horae Gene Therapy Center and The Li Weibo Inst. for Rare Diseases Res., UMass Chan Medical School, Worcester, MA, USA) ,  GERNOUX Gwladys (Horae Gene Therapy Center and The Li Weibo Inst. for Rare Diseases Res., UMass Chan Medical School, Worcester, MA, USA) ,  BLACKWOOD Meghan (Horae Gene Therapy Center and The Li Weibo Inst. for Rare Diseases Res., UMass Chan Medical School, Worcester, MA, USA) ,  MUELLER Christian (Horae Gene Therapy Center and The Li Weibo Inst. for Rare Diseases Res., UMass Chan Medical School, Worcester, MA, USA) ,  TAI Phillip W. L. (Horae Gene Therapy Center and The Li Weibo Inst. for Rare Diseases Res., UMass Chan Medical School, Worcester, MA, USA) ,  KEELER Allison M. (Horae Gene Therapy Center and The Li Weibo Inst. for Rare Diseases Res., UMass Chan Medical School, Worcester, MA, USA) ,  BROWN Robert H., Jr. (Horae Gene Therapy Center and The Li Weibo Inst. for Rare Diseases Res., UMass Chan Medical School, Worcester, MA, USA) ,  GRAY-EDWARDS Heather L. (Horae Gene Therapy Center and The Li Weibo Inst. for Rare Diseases Res., UMass Chan Medical School, Worcester, MA, USA) ,  SENA-ESTEVES Miguel (Horae Gene Therapy Center and The Li Weibo Inst. for Rare Diseases Res., UMass Chan Medical School, Worcester, MA, USA) ,  CATALTEPE Oguz (Dep. of Neurosurgery, UMass Chan Medical School, Worcester, MA, USA) ,  MOSER Richard (Dep. of Neurosurgery, UMass Chan Medical School, Worcester, MA, USA) ,  PURI Ajit (Dep. of Radiology, UMass Chan Medical School, Worcester, MA, USA) ,  ABAYAZEED Aly (Dep. of Radiology, UMass Chan Medical School, Worcester, MA, USA) ,  ROHATGI Saurabh (Dep. of Radiology, UMass Chan Medical School, Worcester, MA, USA) ,  VARDAR Zeynep (Dep. of Radiology, UMass Chan Medical School, Worcester, MA, USA) ,  SHAZEEB Mohammed Salman (Dep. of Radiology, UMass Chan Medical School, Worcester, MA, USA) ,  GOUNIS Matthew (Dep. of Radiology, UMass Chan Medical School, Worcester, MA, USA) ,  GRAY-EDWARDS Heather L. (Dep. of Radiology, UMass Chan Medical School, Worcester, MA, USA) ,  BATISTA Ana Rita (Dep. of Neurology, UMass Chan Medical School, Worcester, MA, USA) ,  MCKENNA-YASEK Diane (Dep. of Neurology, UMass Chan Medical School, Worcester, MA, USA) ,  DOUTHWRIGHT Catherine (Dep. of Neurology, UMass Chan Medical School, Worcester, MA, USA) ,  BROWN Robert H., Jr. (Dep. of Neurology, UMass Chan Medical School, Worcester, MA, USA) ,  SENA-ESTEVES Miguel (Dep. of Neurology, UMass Chan Medical School, Worcester, MA, USA) ,  JIANG Xuntian (Dep. of Medicine and Cardiovascular Div., Washington Univ. School of Medicine, St. Louis, MO, USA) ,  SPANAKIS Spiro G. (Departments of Anesthesiology and Perioperative Medicine, UMass Chan Medical School, Worcester, MA, USA) ,  PARZYCH Julia (Departments of Anesthesiology and Perioperative Medicine, UMass Chan Medical School, Worcester, MA, USA) ,  GIBSON Laura (Dep. of Internal Medicine, UMass Chan Medical School, Worcester, MA, USA) ,  FINBERG Robert (Dep. of Internal Medicine, UMass Chan Medical School, Worcester, MA, USA) ,  BARTON Bruce A. (Population and Quantitative Health Sci., UMass Chan Medical School, Worcester, MA, USA) ,  TIFFT Cynthia J. (National Human Genome Res. Inst., National Inst. of Health, Bethesda, MD, USA) ,  EICHLER Florian S. (Dep. of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA) ,  MARTIN Douglas R. (Scott-Ritchey Res. Center, Dep. of Anatomy, Physiology and Pharmacology, Coll. of Veterinary Medicine, Auburn Univ., Auburn, AL, USA)
資料名： Nature Medicine  (Nature Medicine)
巻： 28  号： 2  ページ： 251-259  発行年： 2022年02月 
JST資料番号： W0636A  ISSN： 1078-8956  資料種別： 逐次刊行物 (A)
記事区分： 原著論文  発行国： アメリカ合衆国 (USA)  言語： 英語 (EN)

抄録/ポイント： テイ・サックス病(TSD)は遺伝性の神経疾患で,ヘキソサミニダーゼA(HexA)の欠損によって引き起こされる。今回我々は,2人の乳児TSD患者でのアデノ随伴ウイルス(AAV)遺伝子治療の拡大アクセス(コンパッショネート)試験(IND18225)について報告する。この試験では,安全性を主要評価項目とし,副次評価項目は設定しなかった。患者TSD-001では,生後30か月時にAAVrh8-HEXAとAAVrh8-HEXBの等モル混合物の髄腔内投与を行い,総投与量[1×10¹⁴ベクターゲノム(vg)]の75%は大槽,25%は胸腰椎接合部に投与した。患者TSD-002では,生後7か月時に左右の視床(片側の視床当たり1.5×10¹²vg)と髄腔内注入(3.9×10¹³vg)を組み合わせて投与を行った。どちらの患者も免疫が抑制された。注入手順の耐容性は高く,これまでにベクターに関連する有害事象(AE)は認められていない。脳脊髄液(CSF)のHexA活性はベースラインから上昇し,どちらの患者でも安定状態が持続した。TSD-002では,注射後3か月までに髄鞘形成の進行を伴って疾患が安定化し,乳児TSDの自然歴から一時的に外れたが,治療後6か月の時点で疾患進行が明確になった。TSD-001は,治療前と同じ抗けいれん治療を受けていて,5歳の時点で発作はない状態が続いている。TSD-002は2歳で抗けいれん薬応答性の発作を起こした。この研究は,ヒトTSD患者のAAV遺伝子治療の初期安全性と概念実証データを示している。Copyright Nature Japan KK 2022

シソーラス用語： *遺伝 ,  痙攣 ,  抗痙攣薬 ,  視床 ,  髄液 ,  ヒト ,  乳児 ,  *治療法 ,  *遺伝子療法 ,  ベクター ,  発作 ,  アデノ随伴ウイルス ,  忍容性
準シソーラス用語： 疾患進行 ,  有害事象 , 【Automatic Indexing@JST】

分類 (5件)： 神経の基礎医学  (GN01020W) ,  血液の基礎医学  (GK01020N) ,  分子遺伝学一般  (EC02010J) ,  免疫反応一般  (ED03010T) ,  遺伝子発現  (EC02040Q)

タイトルに関連する用語 (3件)： 遺伝子治療 ,  テイ・サックス病 ,  AAV