TW200418993A - Huntington's disease - Google Patents
Huntington's disease Download PDFInfo
- Publication number
- TW200418993A TW200418993A TW092133160A TW92133160A TW200418993A TW 200418993 A TW200418993 A TW 200418993A TW 092133160 A TW092133160 A TW 092133160A TW 92133160 A TW92133160 A TW 92133160A TW 200418993 A TW200418993 A TW 200418993A
- Authority
- TW
- Taiwan
- Prior art keywords
- epa
- disease
- patients
- ethyl
- repeats
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/106—Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/118—Prognosis of disease development
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/156—Polymorphic or mutational markers
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- Analytical Chemistry (AREA)
- Epidemiology (AREA)
- Zoology (AREA)
- Genetics & Genomics (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Biotechnology (AREA)
- Immunology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Molecular Biology (AREA)
- General Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pathology (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Plant Substances (AREA)
Description
200418993 玖、發明說明： 【發明所屬之技術領域】 本發明係有關亨丁頓舞蹈症。 【先别技術】 予丁頓舞蹈症（HD)為一種在人類4號染色體上由蛋白質 亨丁亭之基因突變所致之致命遺傳疾病。以任何合適醫藥 形式之脂肪酸，二十碳五烯酸^?八）可用以治療hd(如述於 歐洲專利申請案號1 148873)。 【發明内容】 本發明有關HD之治療及基於以下之發現，即EpA之治療 作用特別發生在該等具特殊基因形sHD之病患。 、 本發明提供一種鑑定具HD之病患或在發展11〇危險下之個 體’或特別可能對以任何合適形式之EPA治療有反應者之方 法，及包括之步驟為進行試驗，以測定亨丁亭基因中CAG重 複序列之數目及鏗疋该等具4 5個或更少重複序列之個體。 右個體具少於36個重複序列時，意示為正常個體。在較 佳之試驗中，選定之個體為該等具44個或更少，或36至44 個CAG重複序列者。 "式驗可在取自個體僅供分析目的及不還給個體之樣品上 進行。診斷步驟將在體外分析。 本發明再提供一種治療HD之方法，及一種預防在發展HD 危險下之個體中發展症狀之方法，包括之步驟為測定個體 基因中予丁亭之CAG重複序列數目，及其為45個或更少 ^ ’投予任何生物有效形式之EPA至個體。在較佳之試驗
O:\89\89537.DOC 200418993 中’選定投予EPA之個體為該等具44個或更少，或36至44 個CAG重複序列者。 用於本發明方法之EPA較佳為乙基-EPA。 46個或更多之CAG重複序列數目在投予安慰劑或EPA之 全部處理組間不顯示任何差異。相反及未預期地，罹患HD 而具45個或更少之CAG重複序列數目之病患在投予EPA上 顯示很大的益處。 雖然全部HD病患在相同基因中具有基因異常性，但並非 全部病患具有相同的異常性。亨丁亭之正常基因含有CaG 重複序列之基因，其基因自身編碼聚麩胺酸序列。甚至在 正常個體中，聚麵胺酸序列為可變的長度，但只要其含有 少於36個CAG重複序列及因此聚麵胺酸序列中少於％個麵 胺酸，則個體將正常。然而，當序列含有36個或更多個eAG 重複序列及其後麵胺酸序列時，將發展HD。具HD2病患會 有著自36至多於1〇〇個CAG重複序列。 HD常以動作障礙開始，特別為影響臉部、頭和頸部及四 肢。此些進展及常伴隨著精神異常性及認知損傷，而導致 癡呆。異常性最初由亨丁亭傷害至紋狀體之神經元所致， 但其後會涉及更廣之腦部區域。最後，病患變成臥床不起 及完全不能照顧自己。其常在疾病開始後10至25年内死亡。 CAG重複序列之數目對疾病開始之年齡有著报強的影 響。具僅超過35個數目之病患不會生病直至其50或60多歲 或甚至更老。具超過6〇個重複序列之病患會在青少年或^ 至童年時生病。然而’多數病患傾向在30至5〇歲間生病。
O:\89\89537.DOC 200418993 一旦疾病開始’則對具大數目C AG重複序列之病患有進展 更快之傾向’但在與開始年齡比較下此影響很弱。 CAG重複序列之數目可由基於聚合酶鏈反應（PCR)之診 斷試驗鑑定。此些試驗提供一種堅定之HD診斷及當然可應 用至欲候鈾的病患。然而，在載有Η〇基因危險下及因此遲 早不叮避免會發展疾病之極少數徵候前的病患對試驗很惱 怒。很多具HD徵候之病患亦不去做試驗。不去做試驗之主 要爭議在於對HD並無有效治療，因此正確知道基因之存在 及那是哪一種基因又如何。 HD中二十碳五烯酸乙基酯（乙基-EPA)之臨床試驗已提供 EPA在HD中有益之強烈證據，及而且完全未預期地，cAg 基因測試之值。 具基因確認HD之13 5個病患經進入一年試驗。其隨機接 受乙基-EPA或相同出現安慰劑之2克/天。其在基線、6個月 及12個月時評估統一亨丁頓舞蹈症評分表（UHdrS)之總動 力計分（TMS)次表。UHDRS為標準評分表，其經用以監測 HD之發展。TMS為最可靠、快速及一致改變之UHDRS成 份，其因此適合監測臨床試驗之結果。 一年結束時，TMS之變化在安慰劑組與乙基_epa組中比 較。總之，在乙基-EPA較在安慰劑上有好的結果，但在統 計上不顯著。然而，當病患基於其CAg重複序列數目而成 層時’乙基-EPA之戲劇性效果不適用。具46個或更多CAG 重複序列數目之病患在安慰劑與乙基_EPA間全部不顯示任 何差異。相反地，具低於45個或更少CAG重複序列數目之
O:\89\89537.DOC 200418993 病心·、、、員不自乙基_EPA受益很大。具低於“個或更少CAG重 複序列數目之安慰劑病患惡化約5.3%。相反地，在乙基-EPA 之=同病患組上一年内改進約19·3%。此差異在共變異分析 或X測试上為高度顯著差異的。特別驚人的是在乙基_ερα 上之大多數病患有確實改進之事實。先前希望最佳的為神 、、二退化疾病如HD為緩慢惡化而非任何確實改進。因為乙基 ΕΡΑ組較安慰劑組之病患在—年内改進多於倍，此意 指一年後ΕΡΑ和安慰劑病患由多於4_1/2年之疾病進展來分 開。另一方面，治療之病患已得到至少4_1/2年之有用生命。 相反地，具46個或更多CAG重複序列之病患在乙s_EpA與 安慰劑處理組間不顯示任何差異 較佳地，本發明治療方法及延緩或防止丁頓舞蹈症開始 之方法中，EPA治療本質上經討論於歐洲專利申請案號 1 148873 中。 較佳的在使用純或近乎純EpA和EpA衍生物。dha和有關 脂肪酸不僅不有效，而且會確實降低EpA和其衍生物之效力。 較佳之製備物包括適當可吸收形式之EpA，自其製備物 中存在之全部脂肪酸至少9〇%及較佳至少95%為EpA形式 及其中少於5%及較佳少於3%為二十二碳六烯酸之形式。 較“地，存在之其他脂肪酸中，少於及較佳少於各 分別為AA或DPA-n-3。相同優先權施用會與EPA競爭之任何 其他脂肪酸。 較佳地，聚集物DHA、AA和/或DPA-n-3含量少於1〇%之 存在總脂肪酸，及較佳少於5 %。
O:\89\89537.DOC 200418993 EPA可為乙基-EPA之形式、鋰EPA、單_或雙-或三酸甘油 酯EPA或EPA之任何酯或鹽，或游離酸形式之EpA。EpA亦 可為2-取代衍生物或其他衍生物之形式，其減緩其氧化速 率，此外並不改變其在精神或腦障礙上之生物作用至任何 貫質程度（N· Willumsen等人，BiochimicaBiophysica Acta， 1998， 1369: 193-203)。 EPA可與主要作用在神經傳遞素代謝或受器上之藥物組 合。與EPA製備物共同投予之合適藥物為克洛沙平 (clozapine)及典型和非典型神經安定劑類中之任一，包括氯 丙麻井（chlorpromazine)鹵佩里醇（haloperidol)、里斯佩里酮 (ristperidone) > 歐藍沙平（olanzapine)、色提吲哚 (sertindole)、記普拉西酮（ziprasid〇ne)、佐提平（z〇tepine) 或阿米硫皮里德（amisulpiride)。用以減輕一些亨丁頓舞蹈 症狀之標準抗精神分裂藥物、抗抑鬱劑、鎮定劑及抗癲癇 藥物可與EPA調配物一起投藥。 取自EP申請案號1 148873作為治療亨丁頓舞蹈症之實 例，96%純乙基-EPA之隨機試驗在亨丁頓舞蹈症最後階段 之7位嚴重失能病患中進行。全部需要24小時看顧，有著嚴 重動作障礙，暴躁且部分痴呆。其在雙盲試驗基礎下隨機 接受2克/天之乙基-EPA或2克/天之安慰劑共6個月。6個月期 間4位病患顯示進展性退化，而3位病患逆轉疾病之進程及 顯示具降低異常動作，降低情緒易變性和暴躁之改進及改 進記憶與認知功能。當密碼解開時，發現惡化之4位病患服 用安慰劑，而改進之全部3位病患皆服用乙基_EpA。在二位
O:\89\89537.DOC -9- 200418993 服用乙基-EPA和2位安慰劑之4位病患中，腦部退化在研究 開始與結束時由磁共振造影（MRI)評估。mri允許精確評估 側細室大小，即腦半球内之液體填充空間。當亨丁頓舞蹈 症進展時，側腦室擴大，指示著腦組織之損失。在服用安 慰劑之2位病患中，在6個月内側腦室如預期地擴大。在服 用乙基-EPA之2位病患中，MRI顯示侧腦室大小之降低，指 示著腦組織損失之確實逆轉。 在由異常蛋白質蓄積所致之先前不可治療疾病末期之病 患中此些戲劇性結果展現在神經退化障礙中之乙基_ΕρΑ Φ 值。 本發明在鑑定可能對如此治療有反應之病患中由分析亨 丁 τ基因而k供顯著進展。本發明提供以下優點，即可能 地’鑑定在發展疾病危險下之病患及投予EpA至病患以防止 或延緩疾病症狀之發展。 90%和較佳95%或甚至更純形式之EpA調配物可經熟諳 技藝者所知之傳送系統全部口服投藥，包括軟和硬明膠膠 _ 囊；粉末、錠劑或膠囊形式之微膠囊；固體化合物鋰_epa 之錠劑；或以適當天然或合成乳化劑，包括磷脂質或半乳 糖脂製成之乳化液。化合物亦可以腸外，直接或調配於不 同油或於乳化液或分散液投藥，使用靜脈内、腹膜内、肌 肉内或皮下途徑。使用貼片技術之局部投藥或陰道或直腸 形式之投藥亦在本發明範圍内。 當與用以缓和予丁頓舞蹈症狀之藥物組合時，EPA化合 物和其他藥物可分開投藥，各以其自己之調配物。其可分
O:\89\89537.DOC -10- 200418993 開包裝或以相同之總包裝呈現。或者，使用熟諳技藝者已 之技術EPA和其他藥物可一起調配，使得〇.工克至⑺克/ 天及較佳地G.5克至5克/天之EpA每日劑量與其他藥物之正 常每日劑量一起提供。 當單獨投藥時，有用之EPA每曰劑量可在0.05克至5〇克/ 天軏仫地ο·1克至ίο克/天及極佳地〇·5克至5克/天之範圍 【實施方式】 實例調配物 在以下之各實施例中，產品至少9〇%及較佳地95%或更 純。此很重要於其他脂肪酸將與EPA競爭結合部位及降低其 效力。特別地，脂肪酸如DHA、AA、DPA_n_3分別將以少 於5%及較佳少於3%之濃度存在。如此競爭化合物之總聚集 物必須少於10%及較佳少於5%。此純度之程度亦有用於降 低母天必須消費之物質量，其為幫助精神病患順從性之重 要因子，而缺少順從性為其一個嚴重的問題。 1·由硬或軟明膠製成之膠囊，其含有250毫克、500毫克 或1000毫克之乙基-EPA、三酸甘油酯EPA或其他合適形式 之 EPA。 2.含有250毫克、500毫克或1000毫克鋰-EPA之錠劑，或 含有相似量之硬明膠膠囊。 3 ·乳化液、溶液或分散液，其中链-EPA、乙基-EPA、三 酸甘油酯EPA或其他合適形式之EPA，以美味液體形式製備 供口服投藥。 4.經調配5克EPA化合物之一至其中之栓劑或陰道藥栓。 O:\89\89537.DOC -11 - 200418993 5.含有自10毫克至500毫克/毫升EPA化合物之一之靜脈 内溶液或乳化液。 6 -1 0 ·如實例1 -5，但使用EPA之2-取代衍生物。 11-20·如1-10，但其中EPA化合物與用以治療亨丁頓舞 蹈症狀之經常劑量任何其他藥物一起調配。 O:\89\89537.DOC -12-
Claims (1)
- 200418993 拾、申請專利範園： 1 · 一種鑑定具亨丁頓舞蹈症之病患、或在發展亨丁頓舞蹈 症風險下之個體、或將對以任何生物有效形式之EPA治療 有反應者之方法，包括之步驟為測定亨丁亭（Hutingtin) 基因之CAG重複序列數目，及鑑定該等具45個或更少重 複序列之個體。 2·如申請專利範圍第1項之方法，其中治療包括乙基_EpA之 投藥。 3 · 一種治療予丁頓舞蹈症之方法，包括之步驟為鑑定亨丁 苧基因中具45個或更少CAG重複序列數目之病患，及投 予任何生物有效形式之EPA至病患。 4_種在1展了 丁頓舞蹈症風險下之個體中預防症狀發展 之方法’包括之步驟為鑑定在亨丁亭基因中具45個或更 少C AG重複序列數 J数目之個體，及投予任何生物有效形式 之EPA至個體。 5. 如申請專利範圍第 -EPA形式。 3或4項之方法，其中投予之EPA為乙基 O:\89\89537.DOC 200418993 柒、指定代表圖： (一) 本案指定代表圖為：（無） (二) 本代表圖之元件代表符號簡單說明·· 捌、本案若有化學式時，請揭示最能顯示發明特徵的化學式： (無） O:\89\89537.DOC
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0228079.0A GB0228079D0 (en) | 2002-12-02 | 2002-12-02 | Huntington's Disease |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| TW200418993A true TW200418993A (en) | 2004-10-01 |
| TWI306120B TWI306120B (en) | 2009-02-11 |
Family
ID=9948921
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW092133160A TWI306120B (en) | 2002-12-02 | 2003-11-26 | Method of identifying hungtington's disease patients who will respond to epa treatment and related use of epa |
Country Status (29)
| Country | Link |
|---|---|
| US (2) | US20070148643A1 (zh) |
| EP (1) | EP1567667B1 (zh) |
| JP (1) | JP2006507833A (zh) |
| KR (1) | KR20050086895A (zh) |
| CN (1) | CN1717497A (zh) |
| AT (1) | ATE411399T1 (zh) |
| AU (1) | AU2003285519A1 (zh) |
| BR (1) | BR0316969A (zh) |
| CA (1) | CA2506727A1 (zh) |
| CY (1) | CY1108730T1 (zh) |
| DE (1) | DE60324180D1 (zh) |
| DK (1) | DK1567667T3 (zh) |
| ES (1) | ES2315543T3 (zh) |
| GB (1) | GB0228079D0 (zh) |
| HK (1) | HK1081598A1 (zh) |
| HR (1) | HRP20050493A2 (zh) |
| IS (1) | IS7842A (zh) |
| MX (1) | MXPA05005908A (zh) |
| MY (1) | MY138759A (zh) |
| NO (1) | NO20052955L (zh) |
| NZ (1) | NZ539989A (zh) |
| PL (1) | PL376101A1 (zh) |
| PT (1) | PT1567667E (zh) |
| RU (1) | RU2332209C2 (zh) |
| SI (1) | SI1567667T1 (zh) |
| TW (1) | TWI306120B (zh) |
| UA (1) | UA86582C2 (zh) |
| WO (1) | WO2004050913A1 (zh) |
| ZA (1) | ZA200504003B (zh) |
Families Citing this family (43)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007524674A (ja) * | 2004-01-19 | 2007-08-30 | マーテック・バイオサイエンシーズ・コーポレーション | リーリン欠損症または機能障害およびそれに関連する方法 |
| WO2007123391A1 (en) | 2006-04-20 | 2007-11-01 | Academisch Ziekenhuis Leiden | Therapeutic intervention in a genetic disease in an individual by modifying expression of an aberrantly expressed gene. |
| EP1857548A1 (en) | 2006-05-19 | 2007-11-21 | Academisch Ziekenhuis Leiden | Means and method for inducing exon-skipping |
| NZ574807A (en) | 2006-08-11 | 2011-01-28 | Prosensa Technologies Bv | Methods and means for treating dna repeat instability associated genetic disorders |
| CN101790385A (zh) | 2007-07-12 | 2010-07-28 | 普罗森那技术公司 | 用于使化合物靶向多种选定器官、组织或肿瘤细胞的分子 |
| WO2009008727A2 (en) | 2007-07-12 | 2009-01-15 | Prosensa Technologies B.V. | Molecules for targeting compounds to various selected organs or tissues |
| USRE48468E1 (en) | 2007-10-26 | 2021-03-16 | Biomarin Technologies B.V. | Means and methods for counteracting muscle disorders |
| CN105641700B (zh) | 2007-10-26 | 2021-01-01 | 莱顿教学医院 | 对抗肌肉病症的方式和方法 |
| CN101980726A (zh) | 2008-02-08 | 2011-02-23 | 普罗森那控股公司 | 治疗与dna重复不稳定性相关的遗传病症的方法和装置 |
| EP2119783A1 (en) | 2008-05-14 | 2009-11-18 | Prosensa Technologies B.V. | Method for efficient exon (44) skipping in Duchenne Muscular Dystrophy and associated means |
| EP2334295B1 (en) | 2008-09-02 | 2017-06-28 | Amarin Pharmaceuticals Ireland Limited | Pharmaceutical composition comprising eicosapentaenoic acid and nicotinic acid and methods of using same |
| DK2596786T3 (da) | 2009-02-10 | 2020-02-24 | Amarin Pharmaceuticals Ie Ltd | Anvendelse af eicosapentaensyreethylester til behandling af hypertriglyceridæmi |
| JP2012524540A (ja) | 2009-04-24 | 2012-10-18 | プロセンサ テクノロジーズ ビー．ブイ． | Ｄｍｄを処置するためのイノシンを含むオリゴヌクレオチド |
| NZ624963A (en) | 2009-04-29 | 2016-07-29 | Amarin Pharmaceuticals Ie Ltd | Pharmaceutical compositions comprising epa and a cardiovascular agent and methods of using the same |
| HUE051916T2 (hu) | 2009-04-29 | 2021-04-28 | Amarin Pharmaceuticals Ie Ltd | Stabil gyógyászati készítmény és annak alkalmazási módszerei |
| SG177254A1 (en) | 2009-06-15 | 2012-02-28 | Ian Osterloh | Compositions and methods for lowering triglycerides without raising ldl-c levels in a subject on concomitant statin therapy |
| SG10201405994UA (en) | 2009-09-23 | 2014-10-30 | Amarin Pharmaceuticals Ie Ltd | Pharmaceutical Composition Comprising Omega-3 Fatty Acid And Hydroxy-derivative Of A Statin And Methods Of Using Same |
| WO2011078672A1 (en) | 2009-12-24 | 2011-06-30 | Prosensa Technologies B.V. | Molecule for treating an inflammatory disorder |
| US11712429B2 (en) | 2010-11-29 | 2023-08-01 | Amarin Pharmaceuticals Ireland Limited | Low eructation composition and methods for treating and/or preventing cardiovascular disease in a subject with fish allergy/hypersensitivity |
| AU2011336856A1 (en) | 2010-11-29 | 2013-07-04 | Amarin Pharmaceuticals Ireland Limited | Low eructation composition and methods for treating and/or preventing cardiovascular disease in a subject with fish allergy/hypersensitivity |
| WO2013070735A1 (en) | 2011-11-07 | 2013-05-16 | Amarin Pharmaceuticals Ireland Limited | Methods of treating hypertriglyceridemia |
| US11291643B2 (en) | 2011-11-07 | 2022-04-05 | Amarin Pharmaceuticals Ireland Limited | Methods of treating hypertriglyceridemia |
| EP2800469B1 (en) | 2012-01-06 | 2021-08-25 | Amarin Pharmaceuticals Ireland Limited | Compositions and methods for lowering levels of high-sensitivity (hs-crp) in a subject |
| CN112251436A (zh) | 2012-01-27 | 2021-01-22 | 比奥马林技术公司 | 治疗杜兴型肌营养不良症和贝克型肌营养不良症的具有改善特性的rna调节性寡核苷酸 |
| AU2013282394B2 (en) | 2012-06-29 | 2018-04-26 | Amarin Pharmaceuticals Ireland Limited | Methods of reducing the risk of a cardiovascular event in a subject on statin therapy |
| US20150265566A1 (en) | 2012-11-06 | 2015-09-24 | Amarin Pharmaceuticals Ireland Limited | Compositions and Methods for Lowering Triglycerides without Raising LDL-C Levels in a Subject on Concomitant Statin Therapy |
| US9814733B2 (en) | 2012-12-31 | 2017-11-14 | A,arin Pharmaceuticals Ireland Limited | Compositions comprising EPA and obeticholic acid and methods of use thereof |
| US20140187633A1 (en) | 2012-12-31 | 2014-07-03 | Amarin Pharmaceuticals Ireland Limited | Methods of treating or preventing nonalcoholic steatohepatitis and/or primary biliary cirrhosis |
| US9452151B2 (en) | 2013-02-06 | 2016-09-27 | Amarin Pharmaceuticals Ireland Limited | Methods of reducing apolipoprotein C-III |
| US9624492B2 (en) | 2013-02-13 | 2017-04-18 | Amarin Pharmaceuticals Ireland Limited | Compositions comprising eicosapentaenoic acid and mipomersen and methods of use thereof |
| US9662307B2 (en) | 2013-02-19 | 2017-05-30 | The Regents Of The University Of Colorado | Compositions comprising eicosapentaenoic acid and a hydroxyl compound and methods of use thereof |
| US9283201B2 (en) | 2013-03-14 | 2016-03-15 | Amarin Pharmaceuticals Ireland Limited | Compositions and methods for treating or preventing obesity in a subject in need thereof |
| US20140271841A1 (en) | 2013-03-15 | 2014-09-18 | Amarin Pharmaceuticals Ireland Limited | Pharmaceutical composition comprising eicosapentaenoic acid and derivatives thereof and a statin |
| US10966968B2 (en) | 2013-06-06 | 2021-04-06 | Amarin Pharmaceuticals Ireland Limited | Co-administration of rosiglitazone and eicosapentaenoic acid or a derivative thereof |
| US20150065572A1 (en) | 2013-09-04 | 2015-03-05 | Amarin Pharmaceuticals Ireland Limited | Methods of treating or preventing prostate cancer |
| US9585859B2 (en) | 2013-10-10 | 2017-03-07 | Amarin Pharmaceuticals Ireland Limited | Compositions and methods for lowering triglycerides without raising LDL-C levels in a subject on concomitant statin therapy |
| US10561631B2 (en) | 2014-06-11 | 2020-02-18 | Amarin Pharmaceuticals Ireland Limited | Methods of reducing RLP-C |
| US10172818B2 (en) | 2014-06-16 | 2019-01-08 | Amarin Pharmaceuticals Ireland Limited | Methods of reducing or preventing oxidation of small dense LDL or membrane polyunsaturated fatty acids |
| US10406130B2 (en) | 2016-03-15 | 2019-09-10 | Amarin Pharmaceuticals Ireland Limited | Methods of reducing or preventing oxidation of small dense LDL or membrane polyunsaturated fatty acids |
| TW201900160A (zh) | 2017-05-19 | 2019-01-01 | 愛爾蘭商艾瑪琳製藥愛爾蘭有限公司 | 用於降低腎功能下降之個體中的三酸甘油酯之組合物及方法 |
| US11058661B2 (en) | 2018-03-02 | 2021-07-13 | Amarin Pharmaceuticals Ireland Limited | Compositions and methods for lowering triglycerides in a subject on concomitant statin therapy and having hsCRP levels of at least about 2 mg/L |
| KR102296068B1 (ko) | 2018-09-24 | 2021-09-02 | 애머린 파마슈티칼스 아일랜드 리미티드 | 대상체에서 심혈관 사건의 위험도를 감소시키는 방법 |
| KR20240012390A (ko) | 2021-04-21 | 2024-01-29 | 애머린 파마슈티칼스 아일랜드 리미티드 | 심부전의 위험을 감소시키는 방법 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2116280A1 (en) * | 1993-03-05 | 1994-09-06 | Marcy E. Macdonald | Huntingtin dna, protein and uses thereof |
| CA2216057A1 (en) * | 1997-09-19 | 1999-03-19 | Ridha Joober | Polymorphic cag repeat-containing gene, diagnosis of psychiatric diseases and therapeutic uses thereof |
| GB9901809D0 (en) * | 1999-01-27 | 1999-03-17 | Scarista Limited | Highly purified ethgyl epa and other epa derivatives for psychiatric and neurological disorderes |
| WO2001024781A2 (en) * | 1999-10-07 | 2001-04-12 | Novaneuron Inc. | Gene necessary for striatal function, uses thereof, and compounds for modulating same |
-
2002
- 2002-12-02 GB GBGB0228079.0A patent/GB0228079D0/en not_active Ceased
-
2003
- 2003-11-21 MY MYPI20034492A patent/MY138759A/en unknown
- 2003-11-26 PL PL03376101A patent/PL376101A1/xx unknown
- 2003-11-26 KR KR1020057009802A patent/KR20050086895A/ko not_active Application Discontinuation
- 2003-11-26 UA UAA200505201A patent/UA86582C2/ru unknown
- 2003-11-26 TW TW092133160A patent/TWI306120B/zh active
- 2003-11-26 DE DE60324180T patent/DE60324180D1/de not_active Expired - Lifetime
- 2003-11-26 PT PT03778516T patent/PT1567667E/pt unknown
- 2003-11-26 DK DK03778516T patent/DK1567667T3/da active
- 2003-11-26 BR BR0316969-3A patent/BR0316969A/pt not_active IP Right Cessation
- 2003-11-26 RU RU2005115536/14A patent/RU2332209C2/ru not_active IP Right Cessation
- 2003-11-26 NZ NZ539989A patent/NZ539989A/en unknown
- 2003-11-26 MX MXPA05005908A patent/MXPA05005908A/es active IP Right Grant
- 2003-11-26 US US10/536,927 patent/US20070148643A1/en not_active Abandoned
- 2003-11-26 JP JP2004556479A patent/JP2006507833A/ja active Pending
- 2003-11-26 ES ES03778516T patent/ES2315543T3/es not_active Expired - Lifetime
- 2003-11-26 CA CA002506727A patent/CA2506727A1/en not_active Abandoned
- 2003-11-26 SI SI200331472T patent/SI1567667T1/sl unknown
- 2003-11-26 AU AU2003285519A patent/AU2003285519A1/en not_active Abandoned
- 2003-11-26 AT AT03778516T patent/ATE411399T1/de not_active IP Right Cessation
- 2003-11-26 WO PCT/GB2003/005131 patent/WO2004050913A1/en active Application Filing
- 2003-11-26 EP EP03778516A patent/EP1567667B1/en not_active Expired - Lifetime
- 2003-11-26 CN CNA2003801044204A patent/CN1717497A/zh active Pending
-
2005
- 2005-05-12 IS IS7842A patent/IS7842A/is unknown
- 2005-05-18 ZA ZA200504003A patent/ZA200504003B/en unknown
- 2005-06-02 HR HR20050493A patent/HRP20050493A2/xx not_active Application Discontinuation
- 2005-06-16 NO NO20052955A patent/NO20052955L/no not_active Application Discontinuation
-
2006
- 2006-02-02 HK HK06101406A patent/HK1081598A1/xx not_active IP Right Cessation
-
2009
- 2009-01-14 CY CY20091100029T patent/CY1108730T1/el unknown
- 2009-04-24 US US12/429,825 patent/US20090270504A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| NO20052955L (no) | 2005-06-16 |
| GB0228079D0 (en) | 2003-01-08 |
| HK1081598A1 (en) | 2006-05-19 |
| RU2005115536A (ru) | 2006-01-27 |
| PL376101A1 (en) | 2005-12-12 |
| BR0316969A (pt) | 2005-10-25 |
| HRP20050493A2 (en) | 2005-10-31 |
| KR20050086895A (ko) | 2005-08-30 |
| RU2332209C2 (ru) | 2008-08-27 |
| CA2506727A1 (en) | 2004-06-17 |
| ATE411399T1 (de) | 2008-10-15 |
| PT1567667E (pt) | 2008-11-04 |
| DE60324180D1 (de) | 2008-11-27 |
| ZA200504003B (en) | 2007-01-31 |
| ES2315543T3 (es) | 2009-04-01 |
| IS7842A (is) | 2005-05-12 |
| NZ539989A (en) | 2006-11-30 |
| MY138759A (en) | 2009-07-31 |
| US20070148643A1 (en) | 2007-06-28 |
| SI1567667T1 (sl) | 2009-04-30 |
| EP1567667B1 (en) | 2008-10-15 |
| MXPA05005908A (es) | 2005-12-12 |
| CY1108730T1 (el) | 2014-04-09 |
| DK1567667T3 (da) | 2009-01-12 |
| WO2004050913A1 (en) | 2004-06-17 |
| JP2006507833A (ja) | 2006-03-09 |
| EP1567667A1 (en) | 2005-08-31 |
| US20090270504A1 (en) | 2009-10-29 |
| UA86582C2 (ru) | 2009-05-12 |
| TWI306120B (en) | 2009-02-11 |
| AU2003285519A1 (en) | 2004-06-23 |
| CN1717497A (zh) | 2006-01-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TW200418993A (en) | Huntington's disease | |
| JP7312169B2 (ja) | 遺伝性てんかん性障害の処置に使用するガナキソロン | |
| JP7128536B2 (ja) | 特定の患者集団において神経変性障害を処置する方法 | |
| JP2023071832A (ja) | フェンフルラミンを用いるドゥーゼ症候群の治療方法 | |
| EP2556827A1 (en) | Treatment of neurodegenerative diseases | |
| BRPI0612921A2 (pt) | composições farmacêuticas de um esteróide neuroativo e métodos de uso do mesmo | |
| CN105228622B (zh) | 用于治疗多发性硬化的PPARγ激动剂 | |
| TWI794885B (zh) | 全身紅斑性狼瘡之治療 | |
| CN104583182A (zh) | 用于治疗粘膜炎的组合物和方法 | |
| CA2620274A1 (en) | Methods for the treatment of senile dementia of the alzheimer's type | |
| US10420770B2 (en) | Compositions and methods for treating dementia | |
| TW201605443A (zh) | 治療ｘ染色體脆折症及相關病症的方法 | |
| WO2017049044A1 (en) | Ursodeoxycholic acid and brain disorders | |
| WO2020132522A1 (en) | Treatment of neurodevelopmental disorders | |
| JP6987749B2 (ja) | Ｓｋチャネル阻害剤による学習障害および他の神経障害の治療 | |
| TW202131910A (zh) | 使用mtorc1調節劑的治療方法 | |
| TWI854792B (zh) | 使用金奈米團簇來治療及/或預防淋巴管新生相關疾病的方法 | |
| Puri | Treatment of Huntington’s disease with eicosapentaenoic acid | |
| Liu et al. | Acitretin Treatment Improves a Case of Severe Generalized Epidermodysplasia Verruciformis | |
| Merlini et al. | GP 2.15 EUROSMART: European Spinal Muscular Atrophy Randomised Placebo-Controlled Trial of acetyl-L-carnitine in spinal muscular atrophy | |
| Calvey | Adverse drug reactions |