JP2016534029A - S100に基づく心臓パワー不全の処置 - Google Patents
S100に基づく心臓パワー不全の処置 Download PDFInfo
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Abstract
Description
本明細書で用いる用語は、"A multilingual glossary of biotechnological terms: (IUPAC Recommendations)", H.G.W. Leuenberger, B. Nagel, and H. Koelbl, Eds., Helvetica Chimica Acta, CH-4010 Basel, Switzerland, (1995)に記載されるとおり定義されることが好ましい。
第1態様において、本発明は、心臓疾患を患っているかまたは発症する危険性がある個体において心臓パワーを高めることにより心臓疾患を処置するのに用いるためのS100タンパク質または該S100タンパク質をコードする核酸であって、該個体の心筋中のS100タンパク質の濃度を治療濃度域内にするため増加させる該タンパク質または核酸に関する。したがって、該個体の心筋中のS100タンパク質の濃度を、生物学的または治療的に関連している作用を高める能力を生じる、操作された心筋のS100タンパク質レベルの範囲内にするため増加させる。
V-V-L-I-A-A-L-A-V-M(配列番号:322)、V-V-L-I-A-A-L-A-V-V(配列番号:323)、V-V-L-I-A-A-L-T-A-M(配列番号:324)、V-V-L-I-A-A-L-T-A-V(配列番号:325)、V-V-L-I-A-A-L-T-I-M(配列番号:326)、V-V-L-I-A-A-L-T-I-V(配列番号:327)、V-V-L-M-G-V-L-T-V-A(配列番号:328)、V-V-L-M-G-A-L-A-V-A(配列番号:329)、V-V-L-M-G-A-L-T-A-A(配列番号:330)、V-V-L-M-G-A-L-T-I-A(配列番号:331)、V-V-L-M-G-A-L-T-V-M(配列番号:332)、V-V-L-M-G-A-L-T-V-V(配列番号:333)、V-V-L-M-S-V-L-T-V-A(配列番号:334)、V-V-L-M-S-A-L-A-V-A(配列番号:335)、V-V-L-M-S-A-L-T-A-A(配列番号:336)、V-V-L-M-S-A-L-T-I-A(配列番号:337)、V-V-L-M-S-A-L-T-V-M(配列番号:338)、V-V-L-M-S-A-L-T-V-V(配列番号:339)、V-V-L-M-A-V-L-A-V-A(配列番号:340)、V-V-L-M-A-V-L-T-A-A(配列番号:341)、V-V-L-M-A-V-L-T-I-A(配列番号:342)、V-V-L-M-A-V-L-T-V-M(配列番号:343)、V-V-L-M-A-V-L-T-V-V(配列番号:344)、V-V-L-M-A-A-L-A-A-A(配列番号:345)、V-V-L-M-A-A-L-A-I-A(配列番号:346)、V-V-L-M-A-A-L-A-V-M(配列番号:347)、V-V-L-M-A-A-L-A-V-V(配列番号:348)、V-V-L-V-G-V-L-A-V-A(配列番号:349)、V-V-L-V-G-V-L-T-A-A(配列番号:350)、V-V-L-V-G-V-L-T-I-A(配列番号:351)、V-V-L-V-G-V-L-T-V-M(配列番号:352)、V-V-L-V-G-V-L-T-V-V(配列番号:353)、V-V-L-V-G-A-L-A-A-A(配列番号:354)、V-V-L-V-G-A-L-A-I-A(配列番号:355)、V-V-L-V-G-A-L-A-V-M(配列番号:356)、V-V-L-V-G-A-L-A-V-V(配列番号:357)、V-V-L-V-G-A-L-T-A-M(配列番号:358)、V-V-L-V-G-A-L-T-A-V(配列番号:359)、V-V-L-V-G-A-L-T-I-M(配列番号:360)、V-V-L-V-G-A-L-T-I-V(配列番号:361)、V-V-L-V-S-V-L-A-V-A(配列番号:362)、V-V-L-V-S-V-L-T-A-A(配列番号:363)、V-V-L-V-S-V-L-T-I-A(配列番号:364)、V-V-L-V-S-V-L-T-V-M(配列番号:365)、V-V-L-V-S-V-L-T-V-V(配列番号:366)、V-V-L-V-S-A-L-A-A-A(配列番号:367)、V-V-L-V-S-A-L-A-I-A(配列番号:368)、V-V-L-V-S-A-L-A-V-M(配列番号:369)、V-V-L-V-S-A-L-A-V-A-V(配列番号:370)、V-V-L-V-S-A-L-T-A-M(配列番号:371)、V-V-L-V-S-A-L-T-A-V(配列番号:372)、V-V-L-V-S-A-L-T-I-M(配列番号:373)、V-V-L-V-S-A-L-T-I-V(配列番号:374)、V-V-L-V-A-V-L-A-A-A(配列番号:375)、V-V-L-V-A-V-L-A-I-A(配列番号:376)、V-V-L-V-A-V-L-A-V-M(配列番号:377)、V-V-L-V-A-V-L-A-V-V(配列番号:378)、V-V-L-V-A-V-L-T-A-M(配列番号:379)、V-V-L-V-A-V-L-T-A-V(配列番号:380)、V-V-L-V-A-V-L-T-I-M(配列番号:381)、V-V-L-V-A-V-L-T-I-V(配列番号:382)、V-V-L-V-A-A-L-A-A-M(配列番号:383)、V-V-L-V-A-A-L-A-A-V(配列番号:384)、V-V-L-V-A-A-L-A-I-M(配列番号:385)、V-V-L-V-A-A-L-A-I-V(配列番号:386)、V-V-L-M-A-A-L-T-A-M(配列番号:390)、V-V-L-M-A-A-L-T-A-V(配列番号:391)、V-V-L-M-A-A-L-T-I-M(配列番号:392)、V-V-L-M-A-A-L-T-I-V(配列番号:393)、およびI-V-L-V-A-A-L-T-V-A(配列番号:394)からなる群より選択されるアミノ酸配列を含むまかたはそれらからなる。これらのアミノ酸配列は、本発明によるS100タンパク質の変種または断片に含まれる変力性モチーフの好ましい特定の実施態様である。
正常な心機能を有するマウスにおける心機能を向上させる心筋のS100A1タンパク質発現の範囲は、AAV9介在性ヒトS100A1 cDNAの心筋送達の使用により測定される。心筋S100A1タンパク質レベルを徐々に増加させることに関する心機能を、正常な心筋においてインビボにおける心機能の急で持続的な向上のためのS100A1タンパク質濃度の有効な用量範囲を測定するために、正常な6月齢のC57B/6マウスにおいて評価した。用いられる技術は、全心筋の導入遺伝子発現の漸増のためのAAV9の静脈内適用を用いているVoelkers et al. Circ Res (2011) 108; 27-39;心機能分析のための心エコー検査についてMost et al. JCI (2004) 114; 1550-1563に詳細に記載されている。AAV9-S100A1および対応するコントロールベクターの生成ならびに両導入遺伝子の発現を駆動する心臓特異的プロモーター構成要素の使用が、Pleger et al. Science Translational Medicine (2011) 3, 92ra64に詳細に記載されている。S100A1の過剰発現(2、4、8、20および50倍)は、静脈内のAAV9-S100A1用量(総ウイルス粒子;tvp)5x1010、1x1011、2x1011、5x1011、1x1012にそれぞれ相当する。マウスの心筋中の総S100A1タンパク質量を、実施例4に詳細に記載するとおり、ELISAにより評価した。S100A1濃度を、Most et al. JCI (2004) 114; 1550-1563に記載のとおり、オーダーメイドのウサギ抗S100A1ポリクローナルIgG抗体(SA 5632)を用いてウエスタンブロットにより測定した。心筋湿重量1 g当たりS100A1タンパク質0.83μgは、健常な左心室心筋における正常なS100A1値に等しく、相対比較のために1として設定されている。WBにより評価されたn倍の相対的変化とELISAにより測定された総心筋のS100A1タンパク質間の変換は、第2のX軸により与えられる。図1(左)は、麻酔されたマウスにおける左心室駆出分画率(LV EF%)が、正常なS100A1タンパク質レベルと比較して、心臓のS100A1タンパク質濃度の約4〜6倍の増加に達することを示す(WBによる評価)。心臓のS100A1タンパク質濃度のさらなる増加は、S100A1介在性収縮能力向上の喪失をもたらす。生物学的に有効なS100A1用量は、心筋湿重量1 g当たりS100A1タンパク質0.83〜41.5μgの範囲となり、ピーク作用はS100A1タンパク質3.32μgに関係する(ELISAによる評価)。
心機能障害のあるマウスにおける、ウイルスに基づく再発現の治療濃度域および心筋S100A1タンパク質濃度の増加を評価した。正常なマウスにおけるS100A1用量依存性の結果は、Brinks et al. Circ Res (2010) 107; 1140-1149に詳細に技術的に記載されているとおり、左前冠動脈の一時的な閉塞による実験的心筋梗塞によって心機能障害のあるC57B/6マウスにおけるS100A1再発現の治療濃度域を決定する根拠を提供する。全心筋の導入遺伝子発現の漸増のためのAAV9の静脈内適用のための技術は、Voelkers et al. Circ Res (2011) 108; 27-39に;心機能分析のための心エコー検査は、Most et al. JCI (2004) 114; 1550-1563に詳細に記載されている。AAV9-S100A1および対応するコントロールベクターの生成ならびに両導入遺伝子の発現を駆動する心臓特異的プロモーター構成要素の使用が、Pleger et al. Science Translational Medicine (2011) 3, 92ra64に記載されている。0.7、2、4、8、20および50倍のS100A1再/過剰発現は、静脈内のAAV9-S100A1用量(総ウイルス粒子;tvp)2x1010、5x1010、1x1011、2x1011、5x1011、1x1012にそれぞれ相当する。マウスの心筋中の総S100A1タンパク質量を、実施例4に詳細に記載するとおり、ELISAにより評価した。S100A1濃度を、Most et al. JCI (2004) 114; 1550-1563に記載のとおり、オーダーメイドのウサギ抗S100A1ポリクローナルIgG抗体(SA 5632)を用いてウエスタンブロットにより測定した。心筋湿重量1 g当たりS100A1タンパク質0.83μg未満の総S100A1タンパク質量は、収縮機能障害のある左心室心筋不全を特徴付ける。WBにより評価されたn倍の相対的変化とELISAにより測定された総心筋のS100A1タンパク質間の変換は、第2のX軸により与えられる。
この実施例は、心機能障害のある飼育ブタにおける、ウイルスに基づく再発現の治療濃度域および心筋S100A1タンパク質濃度の増加を詳述する。心不全マウスにおけるS100A1用量依存性の結果は、ヒトの体重、サイズならびに心血管解剖学および病態生理学に近似するS100A1再発現動物モデルの治療濃度域を決定するための根拠を提供する。ブタにおける虚血後心不全は、経皮バルーン閉塞による左冠動脈回旋枝の一時的な閉塞による実験的心筋梗塞によって誘導された。S100A1の再発現および過剰発現は、心臓特異的プロモーター構成要素により制御されたS100A1発現を有するAAV6-S100A1の漸増用量の逆行性静脈内適用により達成された。この目的に用いられた分析技術および分子ツールは、Pleger et al. Science Translational Medicine (2011) 3, 92ra64に詳細に記載されている。AAV6は、心筋S100A1タンパク質濃度の増加を達成するためにより高いAAV6の心筋形質導入効果を利用するAAV9に加えて用いられた。1.6、6、20および50倍のS100A1再/過剰発現は、静脈内のAAV9-S100A1用量(総ウイルス粒子;tvp)の1.5x1013(1.6倍)ならびにAAV6-S100A1用量の1.5x1011(6倍)、1.5x1012(20倍)および1.5x1013(50倍)にそれぞれ相当する。
S100A1の検出を、オーダーメイドの酵素結合免疫吸収測定法(ELISA)により実施した。500 mgの急速凍結した左心室心筋を2.5 mlの氷冷緩衝液(リン酸緩衝生理食塩水(PBS)、pH 7.4、5 mM EGTA、5 mM EDTA、プロテアーゼ阻害剤カクテルIおよびII(Sigma Aldrich))中で、Ultra-Turrax T25を24,000 rpm(5回、30秒間)で用いてホモジナイズした。その後、検体を、5,000rpmで10分間室温において遠心分離した。上清を収集し、-80℃で保管した。ELISA測定について、マイクロタイタープレート(Maxisorb、Nunc)を、捕捉抗体(抗S100oαウサギポリクローナル、abcam、ab11428)でコーティングした。したがって100μlの捕捉抗体溶液(コーティング溶液中2μg/ml、#80050、Alpha Diagnostic International)をウェルに入れ、4℃で一晩インキュベートした。次の日、各ウェルを洗浄溶液(#80080、Alpha Diagnostic International)で3回洗浄した。その後、300μlのブロッキング溶液(#80060、Alpha Diagnostic International)を加えた。3時間インキュベート後、ウェルを洗浄溶液で洗浄した。二重に(in duplicate)100μlの血清検体(検体希釈液(HEPES 23.8g/l、BSA 10g/l、NaCl 5.84g/l、ddH2O中0.1%ツイーン20)中で2:1希釈)を対応するウェルに加え、4℃で一晩インキュベートした。標準曲線を含めた(組み換えヒトS100A1の2.8ng/ml、5.6ng/ml、28ng/ml、56ng/ml、140ng/ml)。次の日、ウェルを洗浄し、PBS(NaCl 8g/l、KCl 0.2g/l、Na2HPO4 1.42g/l、KH2PO4 0.245g/、ddH2O中5%ツイーン20)中で1:5000希釈した100μlの検出抗体(ヒトS100A1親和性の精製ポリクローナルヒツジIgG、R&D Systems)をウェルに加えた。室温で3時間インキュベート後、洗浄し、PBS中で1:1000希釈したホースラディッシュペルオキシダーゼ結合可視化抗体(ロバ抗ヒツジIgG-HRP、sc-2473、Santa Cruz)100μlを加え、プレートを室温で2時間インキュベートした。洗浄後、100μlのTMB(3,3',5,5'-テトラメチルベンジジン)-基質(#80091、Alpha Diagnostic International)を、ウェルにピペットで取った。20分インキュベートした後、50μlの停止溶液(#80100、Alpha Diagnostic International)を加えた。各ウェルの光学密度を、マルチプレートリーダー(Multiskan Spectrum、Thermo Fisher Scientific)で450 nmにおいて測定し、570 nmにおいて補正した。
Claims (35)
- 心臓疾患を患っているかまたは発症する危険性がある個体において心臓パワーを高めることにより心臓疾患を処置するのに用いるためのS100タンパク質または該S100タンパク質をコードする核酸であって、該個体の心筋中のS100タンパク質の濃度を健常な個体における濃度の50倍を超えない程度に増加させる該タンパク質または核酸。
- 個体の心筋中のS100タンパク質の濃度を2〜50倍に増加させる、請求項1に記載のS100タンパク質または該S100タンパク質をコードする核酸。
- 心臓疾患を患っているかまたは発症する危険性がある個体において心臓パワーを高めることにより心臓疾患を処置するのに用いるためのS100タンパク質または該S100タンパク質をコードする核酸であって、該個体の心筋中の濃度を心筋湿重量1 g当たり0.5〜42μgに増加させる該タンパク質または核酸。
- S100タンパク質が、陽性変力作用を示す天然S100タンパク質の断片または変種である、請求項1〜3のいずれかに記載のS100タンパク質または核酸。
- 該断片または変種が、少なくともコアモチーフΦ-X-Ψ-L(式中、ΦおよびΨが各々の場合において独立して選択される疎水性の非芳香族アミノ酸であり、Xが任意のアミノ酸である)を含むアミノ酸配列を含むかまたは該アミノ酸配列からなる、請求項4に記載のS100タンパク質。
- 該天然S100タンパク質が、S100β、S100A1、S100A2、S100A4およびS100A6からなる群より選択される、請求項1〜5のいずれかに記載のS100タンパク質または核酸。
- 核酸がベクターに含まれる、請求項1〜6のいずれかに記載の核酸。
- ベクターが、プラスミドベクター、コスミドベクター、ファージベクター、例えばラムダファージ、線状ファージベクター、ウイルスベクター、ウイルス様粒子、および細菌胞子からなる群より選択される、請求項7に記載の核酸。
- ウイルスベクターが、アデノウイルスベクター、アデノ随伴ウイルス(AAV)ベクター、アルファウイルスベクター、ヘルペスウイルスベクター、麻疹ウイルスベクター、ポックスウイルスベクター、水泡性口内炎ウイルスベクター、レトロウイルスベクターおよびレンチウイルスベクターからなる群より選択される、請求項8に記載の核酸。
- AAVが、AAV6、AAV9からなる群より選択される、請求項9に記載の核酸。
- ベクターが、経口、静脈内、粘膜内、動脈内、筋肉内または歯冠内経路により投与される、請求項7〜10のいずれかに記載の核酸。
- ベクターが、5x1010〜1x1012 tvpの用量で投与されるウイルスベクターである、請求項7〜11のいずれかに記載の核酸。
- 個体が、健常であるか、あるいは心臓障害を患っているかまたは発症する危険性がある、請求項1〜12のいずれかに記載のS100タンパク質または核酸。
- 心臓障害が、筋細胞におけるカルシウム循環不全および/または収縮能力不全に関連している、請求項13に記載のS100タンパク質または核酸。
- 心臓障害が、虚血後収縮機能不全、うっ血性心不全、心原性ショック、敗血症性ショック、心筋梗塞、心筋症、心臓弁の機能不全、および心室障害からなる群より選択される、請求項13〜14のいずれかに記載のS100タンパク質または核酸。
- 心臓障害が、原発性または続発性の心筋症である、請求項13〜15のいずれかに記載のS100タンパク質または核酸。
- 原発性心筋症が、遺伝性心筋症および自然突然変異により生じる心筋症より選択される、請求項16に記載のS100タンパク質または核酸。
- 続発性心筋症が、動脈硬化症により生じる虚血性心筋症、心筋の感染症または中毒症により生じる拡張型心筋症、肺動脈性および/または動脈性高血圧症により生じる高血圧性心臓疾患ならびに心臓弁の疾患から選択される、請求項16に記載のS100タンパク質または核酸。
- 該個体の心臓組織の細胞の少なくとも30%においてS100タンパク質の細胞内レベルを上昇させる、請求項1〜18のいずれかに記載のS100タンパク質または核酸。
- S100タンパク質の細胞内レベルを、少なくとも7日間上昇させる、請求項1〜19のいずれかに記載のタンパク質または核酸。
- 請求項1〜20のいずれかに記載の少なくとも1つのS100タンパク質もしくは核酸またはその医薬的に許容される塩を含み、医薬的に許容される賦形剤、担体および/または希釈剤を含んでいてよい、医薬組成物。
- 対象体において心臓パワーを高めることにより心臓疾患を処置するのに用いるためのS100タンパク質をコードする核酸であって、個体に投与される該核酸を含む、アデノ随伴ウイルス6または9。
- S100タンパク質が、陽性変力作用を示す天然S100タンパク質の断片または変種である、請求項22に記載のアデノ随伴ウイルス。
- 天然S100タンパク質が、S100β、S100A1、S100A2、S100A4およびS100A6からなる群より選択される、請求項23に記載のアデノ随伴ウイルス。
- S100タンパク質の発現が、心臓組織特異的プロモーターにより制御される、請求項22〜24のいずれかに記載のアデノ随伴ウイルス。
- 心臓組織特異的プロモーターが、心臓アクチン・エンハンサー/伸長因子1プロモーター、サイトメガロウイルス・エンハンサー/心室ミオシン軽鎖2プロモーターおよびトロポニンからなる群より選択される、請求項25に記載のアデノ随伴ウイルス。
- 心臓疾患を患っているかまたは発症する危険性がある個体の心筋中のS100タンパク質の濃度を治療濃度域内にするため増加させるための、S100タンパク質または該S100タンパク質をコードする核酸の使用。
- 心筋中の濃度を健常な個体における濃度の50倍を超えない程度に増加させる、請求項27に記載の使用。
- 心筋中の濃度を2〜50倍に増加させる、請求項27に記載の使用。
- 心筋中の濃度を心筋湿重量1 g当たり0.5〜42μgに増加させる、請求項27〜29のいずれかに記載の使用。
- S100タンパク質またはその変力性ペプチドをコードする核酸を含むベクターを投与することにより、心臓疾患を患っているかまたは発症する危険性がある個体の心筋中のS100タンパク質の濃度を治療濃度域内にするため増加させる方法。
- ベクターがウイルスベクターである、請求項31に記載の方法。
- 心臓疾患を患っているかまたは発症する危険性がある個体の心筋中のS100タンパク質の濃度を治療濃度域内にするため増加させることにより該個体を処置する方法。
- 該個体の心筋中のS100またはその変力性ペプチドの濃度を2〜50倍に増加させる、請求項33に記載の方法。
- 該個体の心筋中のS100またはその変力性ペプチドの濃度を心筋湿重量1 g当たり0.5〜42μgに増加させる、請求項33または34に記載の方法。
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Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002542168A (ja) * | 1999-04-07 | 2002-12-10 | フーゴ・アー・カトゥス | 心不全の治療 |
JP2012524034A (ja) * | 2009-04-16 | 2012-10-11 | ウニベルシタットスクリニクム ハイデルベルク | 筋機能増強ペプチド |
JP2013518271A (ja) * | 2010-01-29 | 2013-05-20 | メタノミクス ゲーエムベーハー | 被験体において心不全を診断するための手段及び方法 |
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US5582981A (en) | 1991-08-14 | 1996-12-10 | Gilead Sciences, Inc. | Method for identifying an oligonucleotide aptamer specific for a target |
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Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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Non-Patent Citations (3)
Title |
---|
MOST PATRICK; REMPPIS ANDREW; PLEGER SVEN T; KATUS HUGO A; KOCH WALTER J; ET AL: "S100A1: A NOVEL INOTROPIC REGULATOR OF CARDIAC PERFORMANCE. TRANSITION FROM 以下備考", AMERICAN JOURNAL OF PHYSIOLOGY: REGULATORY, INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, vol. VOL:293, NR:2, JPN5016010421, 1 August 2007 (2007-08-01), US, pages PAGE(S):R568 - R577 * |
PLEGER SVEN T; ET AL: "STABLE MYOCARDIAL-SPECIFIC AAV6-S100A1 GENE THERAPY RESULTS IN CHRONIC 以下備考", CIRCULATION, vol. VOL:115, NR:19, JPN5016010420, 1 May 2007 (2007-05-01), US, pages PAGE(S):2506 - 2515 * |
VOLKERS; LOUGHREY M; MACQUAIDE C M; REMPPIS N; DEGEORGE A; WEGNER B R; FRIEDRICH F V; FINK O; ET AL: "S100A1 DECREASES CALCIUM SPARK FREQUENCY AND ALTERS THEIR SPATIAL CHARACTERISTICS IN 以下備考", CELL CALCIUM, vol. VOL:41, NR:2, JPN5016010422, 28 December 2006 (2006-12-28), GB, pages PAGE(S):135 - 143 * |
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