JP2021532827A - 虚弱性の診断および/または予測のためのバイオマーカー - Google Patents
虚弱性の診断および/または予測のためのバイオマーカー Download PDFInfo
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Abstract
Description
老齢人口は、公衆衛生政策および社会経済開発の成功であり、かつ社会の課題である。社会は、高齢者の社会的ニーズおよび健康上のニーズを持続可能な方法で考慮しつつ、高齢者の福祉および社会的参加、ならびに高齢者に対するサービスの提供を確保しなければならない。加齢に伴って一連の生理学的変化が生じ、環境の要求に対する適応が徐々に失われ、脆弱性が増大する。老齢人口の問題の最も深刻な発現は、虚弱性の臨床症状である。
虚弱性基質の生物学的基礎を理解するための虚弱性の分子マーカーを同定すること、ならびに、その適切な同定および検出のための単純、迅速、安価、確実および定量可能な機器を有することは、現在、革新的かつ工業的な潜在性を以て関心が高まっている分野である。この点に関して、本発明者らは、対象における虚弱性の診断および/または予測に有用なバイオマーカーを同定した。具体的には、本発明のバイオマーカーは、EGR1遺伝子および/またはその発現産物もしくはタンパク質に関する。
(a)前記個体の単離された生物学的試料におけるEGR1バイオマーカーの遺伝子および/またはタンパク質の発現レベルを定量化すること、および、
(b)工程(a)において得られた発現レベルを参照値と比較すること、
を含み、
前記バイオマーカーについての前記参照値に対する、患者の前記試料におけるEGR1バイオマーカーの発現レベルの増加は、虚弱性を有すること、または罹患しやすいことを示す。
〔図1〕分析した患者(n=26)の試料における虚弱性の罹患率を示すグラフであり、分析した試料において、男性に対して虚弱な女性の数の有意な増加を観察した(p<0.001)。
本発明は、本発明の産物の有効性を明らかにする、本発明者らによって行われた試験によって、以下に説明される。
プライマリーケアリサーチユニットは、Guipuzcoa州(スペイン)のコミュニティから1000人の対象のコホートを形成した。具体的には、対象は、OSI BidasoaおよびOSI Donostialdeaに由来し、関係のプライマリーケア専門家に参加するように招待された。インフォームドコンセントを与えた後、彼らは、1回の対面インタビューを依頼され、計画された基礎評価が行われた。当該基礎評価は、社会人口統計学的および健康状態データ(KOS)の収集、人体計測の測定、TilburgおよびBarthel試験アンケート、ならびにTime Up and Goおよび歩行速度などの機能遂行試験を含む。さらに、現在の共疾病率、慢性的な処方、ならびに転倒の発生および医療サービスの使用に関する情報を、彼らの医療記録に基づいて得た。得られた結果は、対象の56%が女性であり、コホートの平均年齢は83歳であることを確認した。
細胞培養物、特に線維芽細胞の連続継代による維持は、老化や虚弱性の進行が伴う分子的および生理学的レベルに近いストレスを細胞内に生み出す。これを考慮し、30〜50歳の大人の対象の試料から得られたインビトロ線維芽細胞培養物における、虚弱性バイオマーカーであるEGR1、DDX11L1、hsa−miR−454の発現を解析した。
Claims (14)
- 対象における虚弱性のインビトロ診断および/または予測のための、単離された生物学的試料におけるEGR1バイオマーカーの発現レベルの使用。
- DDX11L1、miR−454および/またはそれらの任意の組み合わせからなるリストから選択される少なくとも1つのバイオマーカーの発現レベルをさらに含む、請求項1に記載の使用。
- CD69、PTEN、JUN、CISH、DDX11L10、LOC101929775、LOC644172、NSF、TRAJ17、TRAJ19、TRAV8−3、CD40LG、CLDN12、CNTNAP3、CNTNAP3B、CSRNP1、CTSLP8、CXCL8、G0S2、GCNT4、GJB6、IGHV2−26、LOC100505530、LOC105378916、miR−3941、miR−487A、miR−626、MTRNR2L2、RLN1、TIA1、TRAJ14、TRAJ16、TRAJ48、TRAV16、TRBV3−1、および/またはそれらの任意の組み合わせからなるリストから選択される少なくとも1つのバイオマーカーの発現レベルをさらに含む、請求項1または2に記載の使用。
- 前記単離された生物学的試料は、血液、血漿、血清または尿試料からなるリストから選択される、請求項1〜3のいずれか1項に記載の使用。
- 前記単離された生物学的試料は、血液であり、好ましくは末梢血単核細胞である、請求項4に記載の使用。
- 個体における虚弱性の診断および/または予測のための、インビトロ方法であって、
(a)前記個体の単離された生物学的試料におけるEGR1バイオマーカーの発現レベルを定量化すること、および、
(b)工程(a)において得られた発現レベルを参照値と比較すること、
を含み、
前記バイオマーカーについての前記参照値に対する、患者の前記試料におけるEGR1バイオマーカーの発現レベルの増加は、虚弱性に罹患していること、または罹患しやすいことを示す、インビトロ方法。 - 工程(a)において、DDX11L1、miR−454、および/またはそれらの任意の組み合わせからなるリストから選択される少なくとも1つのバイオマーカーの発現レベル、好ましくはDDX11L1およびmiR−454バイオマーカーのセットの発現レベルを定量化することをさらに含み、
前記バイオマーカーについての前記参照値に対する、患者の前記試料におけるDDX11L1およびmiR−454バイオマーカーの発現レベルの減少は、虚弱性に罹患していること、または罹患しやすいことを示す、請求項6に記載のインビトロ方法。 - 工程(a)において、CD69、PTEN、JUN、CISH、DDX11L10、LOC101929775、LOC644172、NSF、TRAJ17、TRAJ19、TRAV8−3、CD40LG、CLDN12、CNTNAP3、CNTNAP3B、CSRNP1、CTSLP8、CXCL8、G0S2、GCNT4、GJB6、IGHV2−26、LOC100505530、LOC105378916、miR−3941、miR−487A、miR−626、MTRNR2L2、RLN1、TIA1、TRAJ14、TRAJ16、TRAJ48、TRAV16、TRBV3−1、および/またはそれらの任意の組み合わせからなるリストから選択される少なくとも1つのバイオマーカーの発現レベル、好ましくはバイオマーカーCD69、PTEN、JUN、CISH、DDX11L10、LOC101929775、LOC644172、NSF、TRAJ17、TRAJ19、TRAV8−3、CD40LG、CLDN12、CNTNAP3、CNTNAP3B、CSRNP1、CTSLP8、CXCL8、G0S2、GCNT4、GJB6、IGHV2−26、LOC100505530、LOC105378916、miR−3941、miR−487A、miR−626、MTRNR2L2、RLN1、TIA1、TRAJ14、TRAJ16、TRAJ48、TRAV16、およびTRBV3−1のセットの発現レベルを定量化することをさらに含む、請求項6〜7のいずれか1項に記載のインビトロ方法。
- 前記参照値は、頑強な個体の単離された生物学的試料における前記バイオマーカーの発現レベルに対応する、請求項5〜8のいずれか1項に記載のインビトロ方法。
- 工程(a)の前記単離された生物学的試料は、血液、血漿、血清または尿試料である、請求項5〜9のいずれか1項に記載のインビトロ方法。
- 前記単離された生物学的試料は、血液であり、好ましくは末梢血単核細胞である、請求項10に記載のインビトロ方法。
- 個体における虚弱性の診断および/または予測のための、単離された生物学的試料におけるEGR1バイオマーカーの発現レベルを検出することができるプライマー、プローブおよび/または抗体を含む、キットまたはデバイス。
- DDX11L1、miR−454、CD69、PTEN、JUN、CISH、DDX11L10、LOC101929775、LOC644172、NSF、TRAJ17、TRAJ19、TRAV8−3、CD40LG、CLDN12、CNTNAP3、CNTNAP3B、CSRNP1、CTSLP8、CXCL8、G0S2、GCNT4、GJB6、IGHV2−26、LOC100505530、LOC105378916、miR−3941、miR−487A、miR−626、MTRNR2L2、RLN1、TIA1、TRAJ14、TRAJ16、TRAJ48、TRAV16およびTRBV3−1、ならびに/またはそれらの任意の組み合わせからなるリストから選択される少なくとも1つのバイオマーカーの発現レベルを検出することができるプライマー、プローブおよび/または抗体をさらに含む、請求項12に記載のキットまたはデバイス。
- 個体における虚弱性のインビトロ診断および/または予測のための、請求項12〜13のいずれか1項に記載のキットまたはデバイスの使用。
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