JP5739898B2 - 心疾患マーカーとしての尿中トリアオシルセラミド(gb3) - Google Patents
心疾患マーカーとしての尿中トリアオシルセラミド(gb3) Download PDFInfo
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- JP5739898B2 JP5739898B2 JP2012540024A JP2012540024A JP5739898B2 JP 5739898 B2 JP5739898 B2 JP 5739898B2 JP 2012540024 A JP2012540024 A JP 2012540024A JP 2012540024 A JP2012540024 A JP 2012540024A JP 5739898 B2 JP5739898 B2 JP 5739898B2
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B10/00—Other methods or instruments for diagnosis, e.g. instruments for taking a cell sample, for biopsy, for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
- A61B10/0045—Devices for taking samples of body liquids
- A61B10/0051—Devices for taking samples of body liquids for taking saliva or sputum samples
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B10/00—Other methods or instruments for diagnosis, e.g. instruments for taking a cell sample, for biopsy, for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
- A61B10/0045—Devices for taking samples of body liquids
- A61B10/0058—Devices for taking samples of body liquids for taking sperm samples
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B10/00—Other methods or instruments for diagnosis, e.g. instruments for taking a cell sample, for biopsy, for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
- A61B10/0045—Devices for taking samples of body liquids
- A61B10/007—Devices for taking samples of body liquids for taking urine samples
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B10/00—Other methods or instruments for diagnosis, e.g. instruments for taking a cell sample, for biopsy, for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
- A61B10/0045—Devices for taking samples of body liquids
- A61B2010/0061—Alimentary tract secretions, e.g. biliary, gastric, intestinal, pancreatic secretions
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/88—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
- G01N2030/8809—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample
- G01N2030/8813—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample biological materials
- G01N2030/8831—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample biological materials involving peptides or proteins
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Epidemiology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
Description
(i)前記ヒト対象から前記尿サンプルを入手し、ろ過紙に配置するステップ;(ii) 前記ろ過紙に配置した前記尿サンプルを乾燥するステップ;(iii) 前記乾燥した尿サンプルをメタノールで抽出するステップ;(iv) 前記抽出した尿サンプルの一部を、メタノール中に既知のGb3濃度を含む放射標識された標準溶液と共にLC−MSシステムに注入するステップ;(v)前記尿サンプル及び前記標準溶液中のGb3をメタノール/水勾配で溶出するステップ;(vi) 前記LC−MSシステムの質量スペクトルから、前記尿サンプル及び前記標準溶液中のGb3の1又は2以上のピークを入手するステップ;(vii) 前記尿サンプル及び前記標準溶液中の標識されたGb3の前記1又は2以上のピークの保持時間に対するピーク面積をプロットして、検量線を作成するステップ;(viii)前記検量線から前記尿サンプル中のGb3レベルを計算するステップ;及び(ix) 前記尿サンプル中のGb3のレベルが、正常な閾値を超える場合に、心疾患、心臓病、又は心疾患のリスク因子の存在を判定するステップであって、前記正常な閾値が200ng/mlであるステップ。
(i)前記ヒト対象から前記生体サンプルを入手し、基質に配置するステップであって、前記基質が、ろ過紙、ろ過器、膜、ビーズ、粒子、有機樹脂、マイクロタイタープレート、及びスライドからなる群より選択されるステップ;(ii) 前記基質に配置された前記生体サンプルを乾燥するステップ;(iii) 前記乾燥した生体サンプルを適切な有機溶媒で抽出するステップ;(iv) 前記抽出した生体サンプルの一部を、前記有機溶媒中に既知の濃度の糖脂質又はスフィンゴ糖脂質を有する標準溶液と共にLC−MSシステムに注入するステップ;(v)前記生体サンプル及び前記標準溶液中の前記糖脂質又はスフィンゴ糖脂質を、適切な溶媒勾配で溶出するステップ;(vi) 前記LC−MSシステムの質量スペクトルから、前記生体サンプル及び前記標準溶液中の糖脂質又はスフィンゴ糖脂質の1又は2以上のピークを得るステップ;(vii) 前記生体サンプル及び前記標準溶液中の糖脂質又はスフィンゴ糖脂質の前記1又は2以上のピークの保持時間に対するピーク面積をプロットして、検量線を作成するステップ;及び(viii) 前記検量線から1又は2以上の糖脂質又はスフィンゴ糖脂質の濃度を計算して、前記生体サンプル中の1又は2以上の糖脂質又はスフィンゴ糖脂質の存在を検出するステップ。
本発明者らは、ろ紙カード上で乾燥した尿中の異なる脂肪酸成分を有するグロボトリアオシルセラミド(Gb3)のアイソフォームの定量に、超高速液体クロマトグラフィ(UPLC)タンデム質量分析(MS/MS)を用いた。5×5cmの表面積のろ紙で乾燥させた1mlの尿を、C17−Gb3を内部標準として用いてメタノールで抽出した。Gb3アイソフォームをクロマトグラフで分離するために、10マイクロリットルをAcquity UPLCに注入した。メタノール/水高速勾配を用いて、C8 BEH、1×50mm、1.7μm UPLCカラム、60℃で、カラム再平衡を含む合計ランタイム3分で行った。多重反応モニタリング転移は、C17−Gb3アイソフォームには、m/z 1060→898であり、m/1046→884、1074→912、1102→940、1128→966、1130→968、1156→994、1158→996、1174→1012が8つの主要なGb3アイソフォームを包含する。Gb3は、エレクトロスプレー陽イオン化法を使用したQuattro Premier MS/MSで分析した。アイソフォームのMRMクロマトグラフィのピーク面積は、尿1mlあたりのGb3ナノグラムを計算するための標準曲線と使用した。
United States Patent No. 7,445,886: Macrophage migration inhibitory factor as a marker for cardiovascular risk.
United States Patent Application No. 20040132688: Plasma glucosylceramide deficiency as risk factor for thrombosis and modulator of anticoagulant protein C.
1 http://www.medicalnewstoday.com/articles/71159.php
2 Johannes M. Aerts, Johanna E. Groener, Sijmen Kuiper, Wilma E. Donker-Koopman Anneke Strijland, Roelof Ottenhoff, Cindy van Roomen, Mina Mirzaian, Frits A. Wijburg, Gabor E. Linthorst, Anouk C. Vedder, Saskia M. Rombach, Josanne Cox-Brinkman, Pentti Somerharju‡, Rolf G. Boot, Carla E. Hollak, Roscoe O. Brady, and Ben J. Poorthuis, (2008), “Elevated globotriaosylsphingosine is a hallmark of Fabry disease”, PNAS, 105(8), 2812-2817.
Claims (4)
- 以下のステップを含む、尿サンプル中のグロボトリアオシルセラミド(Gb3)レベルを計算して、健康なヒト対象、非ファブリー病患者、非ファブリー病の心臓病患者、及びファブリー病に対する遺伝的素因を有さない対象から選択されるヒト対象における心疾患又は心疾患のリスク因子の存在をスクリーニングする方法:
前記ヒト対象から前記尿サンプルを入手し、ろ過紙に配置するステップ;
前記ろ過紙に配置した前記尿サンプルを乾燥するステップ;
前記乾燥した尿サンプルをメタノールで抽出するステップ;
前記抽出した尿サンプルの一部を、メタノール中に既知のGb3濃度を含む放射標識された標準溶液と共にLC−MSシステムに注入するステップ;
前記尿サンプル及び前記標準溶液中のGb3をメタノール/水勾配で溶出するステップ;
前記LC−MSシステムから、質量スペクトル中の前記尿サンプル及び前記標準溶液中のGb3の1又は2以上のピークを入手するステップ;
前記尿サンプル及び前記標準溶液中の標識されたGb3の前記1又は2以上のピークの保持時間に対するピーク面積をプロットして、検量線を作成するステップ;
前記検量線から前記尿サンプル中のGb3レベルを計算するステップ;及び
前記尿サンプル中のGb3のレベルが、正常な閾値を超える場合に、心疾患、又は心疾患のリスク因子の存在を判定するステップであって、前記正常な閾値が200ng/mlであるステップ。 - 尿サンプル中のGb3レベルと正常な閾値との比較に基づいて、ヒト対象に、心臓血管系リスク測定基準を与えるステップをさらに含む、請求項1に記載の方法。
- 心臓血管系リスク測定基準が、ヒト対象の尿サンプル中のGb3のレベルに比例する、請求項2に記載の方法。
- 心疾患が、肥大性心筋症、リズム及び伝導系障害、冠動脈疾患、不整脈、伝導ブロック、及び弁膜症からなる群より選択される、請求項1〜3のいずれかに記載の方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US26183109P | 2009-11-17 | 2009-11-17 | |
US61/261,831 | 2009-11-17 | ||
PCT/US2010/057112 WO2011063048A2 (en) | 2009-11-17 | 2010-11-17 | Urinary triaosylceramide (gb3) as a marker of cardiac disease |
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JP2014224123A Division JP2015071609A (ja) | 2009-11-17 | 2014-11-04 | 心臓病マーカーとしての尿中トリアオシルセラミド(gb3) |
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JP2013511726A JP2013511726A (ja) | 2013-04-04 |
JP5739898B2 true JP5739898B2 (ja) | 2015-06-24 |
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JP2012540024A Expired - Fee Related JP5739898B2 (ja) | 2009-11-17 | 2010-11-17 | 心疾患マーカーとしての尿中トリアオシルセラミド(gb3) |
JP2014224123A Pending JP2015071609A (ja) | 2009-11-17 | 2014-11-04 | 心臓病マーカーとしての尿中トリアオシルセラミド(gb3) |
JP2016206971A Pending JP2017061477A (ja) | 2009-11-17 | 2016-10-21 | 心臓病マーカーとしての尿中トリアオシルセラミド(gb3) |
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JP2014224123A Pending JP2015071609A (ja) | 2009-11-17 | 2014-11-04 | 心臓病マーカーとしての尿中トリアオシルセラミド(gb3) |
JP2016206971A Pending JP2017061477A (ja) | 2009-11-17 | 2016-10-21 | 心臓病マーカーとしての尿中トリアオシルセラミド(gb3) |
Country Status (8)
Country | Link |
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US (2) | US9066939B2 (ja) |
EP (2) | EP2502068B1 (ja) |
JP (3) | JP5739898B2 (ja) |
AR (1) | AR079057A1 (ja) |
CA (1) | CA2781277C (ja) |
ES (2) | ES2568610T3 (ja) |
TW (1) | TW201142297A (ja) |
WO (1) | WO2011063048A2 (ja) |
Families Citing this family (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2533050B3 (en) | 2006-05-16 | 2015-06-24 | Amicus Therapeutics, Inc. | Treatment Options For Fabry Disease |
EP2946785B1 (en) | 2008-02-12 | 2018-10-24 | Amicus Therapeutics, Inc. | Method to predict response to pharmacological chaperone treatment of diseases |
US20120283290A1 (en) * | 2011-05-06 | 2012-11-08 | Amicus Therapeutics Inc. | Quantitation of gl3 in urine |
EP2592423A1 (en) * | 2011-11-08 | 2013-05-15 | Zora Biosciences OY | Lipidomic biomarkers for the prediction of cardiovascular outcomes in coronary artery disease patients not undergoing statin treatment |
EP2592422A1 (en) * | 2011-11-08 | 2013-05-15 | Zora Biosciences OY | Lipidomic biomarkers for the prediction of cardiovascular outcomes in coronary artery disease patients undergoing statin treatment |
WO2014012043A1 (en) * | 2012-07-13 | 2014-01-16 | Baylor Research Institute | Urinary triaosylceramide (gb3) as a risk factor in non-fabry heart disease subjects |
KR101644586B1 (ko) * | 2014-11-18 | 2016-08-02 | 상명대학교서울산학협력단 | 인체 미동에 의한 hrp 기반 사회 관계성 측정 방법 및 시스템 |
KR102631805B1 (ko) | 2017-05-30 | 2024-01-31 | 아미쿠스 세라퓨틱스, 인코포레이티드 | 신장 손상을 갖는 파브리 환자를 치료하는 방법 |
CN109870515B (zh) * | 2017-12-01 | 2021-12-24 | 中国科学院大连化学物理研究所 | 一种基于中药色谱-质谱高维图像数据库的中药识别方法 |
WO2019157047A1 (en) | 2018-02-06 | 2019-08-15 | Amicus Therapeutics, Inc. | Use of migalastat for treating fabry disease in pregnant patients |
JP2022508322A (ja) * | 2018-12-06 | 2022-01-19 | ゾラ バイオサイエンシーズ オサケ ユキチュア | 心血管イベントに対するバイオマーカー |
CN114423428A (zh) | 2019-08-07 | 2022-04-29 | 阿米库斯治疗学公司 | 治疗在gla基因中具有突变的患者的法布里病的方法 |
US11623916B2 (en) | 2020-12-16 | 2023-04-11 | Amicus Therapeutics, Inc. | Highly purified batches of pharmaceutical grade migalastat and methods of producing the same |
Family Cites Families (10)
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US20020095135A1 (en) | 2000-06-19 | 2002-07-18 | David Meeker | Combination enzyme replacement, gene therapy and small molecule therapy for lysosomal storage diseases |
US6451611B1 (en) * | 2000-07-28 | 2002-09-17 | Statens Serum Institute | Quantitative analysis of hexose-monophosphates from biological samples |
DE60217835D1 (en) | 2001-02-28 | 2007-03-15 | John H Griffin | Plasmaglucosylceramiddefizienz als risikofaktor für thrombose und modulator von anticoagulant protein c |
GB0128498D0 (en) * | 2001-11-28 | 2002-01-23 | Inst Of Child Health | International standards for sphingolipids |
US7446098B2 (en) * | 2003-02-18 | 2008-11-04 | Mount Sinai School Of Medicine Of New York University | Combination therapy for treating protein deficiencies |
US7445886B2 (en) | 2003-09-10 | 2008-11-04 | Board Of Regents, The University Of Texas System | Macrophage migration inhibitory factor as a marker for cardiovascular risk |
WO2007106816A2 (en) * | 2006-03-13 | 2007-09-20 | Perkinelmer Las, Inc. | Substrates and internal standards for mass spectroscopy detection |
EP2533050B3 (en) * | 2006-05-16 | 2015-06-24 | Amicus Therapeutics, Inc. | Treatment Options For Fabry Disease |
EP2142197A4 (en) * | 2007-03-30 | 2010-11-10 | Amicus Therapeutics Inc | PROCESS FOR THE TREATMENT OF FABRY DISEASE USING PHARMACOLOGICAL CHAPERONS |
EP2150254A4 (en) * | 2007-04-26 | 2010-11-10 | Amicus Therapeutics Inc | DOSAGES FOR THE TREATMENT OF LYSOSOMAL STORAGE DISEASES WITH PHARMACOLOGICAL CHAPTERONES |
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2010
- 2010-11-17 EP EP10832140.7A patent/EP2502068B1/en not_active Not-in-force
- 2010-11-17 CA CA2781277A patent/CA2781277C/en not_active Expired - Fee Related
- 2010-11-17 AR ARP100104249A patent/AR079057A1/es unknown
- 2010-11-17 JP JP2012540024A patent/JP5739898B2/ja not_active Expired - Fee Related
- 2010-11-17 US US12/948,693 patent/US9066939B2/en not_active Expired - Fee Related
- 2010-11-17 ES ES10832140.7T patent/ES2568610T3/es active Active
- 2010-11-17 WO PCT/US2010/057112 patent/WO2011063048A2/en active Application Filing
- 2010-11-17 EP EP15201785.1A patent/EP3028701B1/en active Active
- 2010-11-17 TW TW099139568A patent/TW201142297A/zh unknown
- 2010-11-17 ES ES15201785T patent/ES2768995T3/es active Active
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2014
- 2014-11-04 JP JP2014224123A patent/JP2015071609A/ja active Pending
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2015
- 2015-06-03 US US14/729,630 patent/US9750732B2/en active Active
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- 2016-10-21 JP JP2016206971A patent/JP2017061477A/ja active Pending
Also Published As
Publication number | Publication date |
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WO2011063048A3 (en) | 2011-09-15 |
EP2502068A4 (en) | 2014-05-21 |
WO2011063048A2 (en) | 2011-05-26 |
TW201142297A (en) | 2011-12-01 |
CA2781277A1 (en) | 2011-05-26 |
US20150342939A1 (en) | 2015-12-03 |
EP2502068A2 (en) | 2012-09-26 |
AR079057A1 (es) | 2011-12-21 |
EP3028701B1 (en) | 2019-11-13 |
US20110172271A1 (en) | 2011-07-14 |
JP2013511726A (ja) | 2013-04-04 |
EP2502068B1 (en) | 2016-02-10 |
US9750732B2 (en) | 2017-09-05 |
JP2015071609A (ja) | 2015-04-16 |
ES2568610T3 (es) | 2016-05-03 |
CA2781277C (en) | 2018-01-09 |
ES2768995T3 (es) | 2020-06-24 |
EP3028701A1 (en) | 2016-06-08 |
US9066939B2 (en) | 2015-06-30 |
JP2017061477A (ja) | 2017-03-30 |
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