JPWO2020049135A5 - - Google Patents

Download PDF

Info

Publication number
JPWO2020049135A5
JPWO2020049135A5 JP2021512725A JP2021512725A JPWO2020049135A5 JP WO2020049135 A5 JPWO2020049135 A5 JP WO2020049135A5 JP 2021512725 A JP2021512725 A JP 2021512725A JP 2021512725 A JP2021512725 A JP 2021512725A JP WO2020049135 A5 JPWO2020049135 A5 JP WO2020049135A5
Authority
JP
Japan
Prior art keywords
lnc
tcons
lncrna
signature
cognitive impairment
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
JP2021512725A
Other languages
Japanese (ja)
Other versions
JP2022501016A (en
Publication date
Application filed filed Critical
Priority claimed from PCT/EP2019/073775 external-priority patent/WO2020049135A1/en
Publication of JP2022501016A publication Critical patent/JP2022501016A/en
Publication of JPWO2020049135A5 publication Critical patent/JPWO2020049135A5/ja
Priority to JP2024021135A priority Critical patent/JP2024073440A/en
Pending legal-status Critical Current

Links

Claims (11)

認知障害を有するか、または発症するリスクがある対象における、限定されるものではないが、アルツハイマー病を含む認知障害の診断を補助するための方法であって、
（ａ）前記対象から単離された生体試料中で、表１～６に列挙されるｌｎｃＲＮＡから選択される少なくとも１つのｌｎｃＲＮＡを含むか、またはそれからなるｌｎｃＲＮＡシグナチャー中の発現レベルを検出すること；
（ｂ）試料中での発現レベルと、参照中での発現レベルとを比較すること
を含み、
参照中でのレベルと比較した試料中での発現レベルの増加または減少が、認知障害を有するか、または認知障害を発症するリスクがある対象を同定する、方法。
Figure 2020049135000001
Figure 2020049135000002
Figure 2020049135000003
Figure 2020049135000004
Figure 2020049135000005
Figure 2020049135000006
 A method for aiding diagnosis of cognitive impairment, including but not limited to Alzheimer's disease, in a subject having or at risk of developing cognitive impairment, comprising:
(a ) detecting in a biological sample isolated from said subject the level of expression in a lncRNA signature comprising or consisting of at least one lncRNA selected from lncRNAs listed in Tables 1-6 ;
( b ) comparing the level of expression in the sample with the level of expression in a reference;
A method wherein an increase or decrease in expression levels in a sample compared to levels in a reference identifies a subject with or at risk of developing cognitive impairment.
Figure 2020049135000001
Figure 2020049135000002
Figure 2020049135000003
Figure 2020049135000004
Figure 2020049135000005
Figure 2020049135000006
 ｌｎｃＲＮＡシグナチャーが、５４のｌｎｃＲＮＡ（ｌｎｃ－ＡＮＡＰＣ１１－２：８、ｌｎｃ－ＣＬＬＵ１－２：６、ｌｎｃ－ＫＬＨＬ３６－２：２、ｌｎｃ－ＬＲＲＣ１０－１：１、ｌｎｃ－ＲＭＤＮ２－３：２４、ｌｎｃ－ＳＭＮ２－４：２、ｌｎｃ－ＳＰＲＹＤ３－１：１７、ｌｎｃ－ＵＳＰ４７－２：１、ｌｎｃ－ＺＣ３Ｈ１２Ｂ－１：５、ＴＣＯＮＳ＿０００１９７９８、ＴＳＰＯＡＰ１－ＡＳ１：３９、ＴＣＯＮＳ＿０００３５０９３、ｌｎｃ－ＯＣＭ－３：４、ｌｎｃ－ＫＩＦ１４－１：２、ＰＣＢＰ１－ＡＳ１：３０２、ｌｎｃ－ＣＡ６－８：１、ＮＥＡＴ１：２２、ｌｎｃ－ＣＡ６－８：２、ＳＴＡＲＤ７－ＡＳ１：５、ｌｎｃ－ＩＬ３１ＲＡ－１：１、ｌｎｃ－ＡＮＫＲＤ３６－１：４、ｌｎｃ－ＡＴＰ６ＡＰ２－１３：１、ｌｎｃ－ＳＯＣＳ６－１０：１、ｌｎｃ－ＣＤＩＰＴ－２：１、ｌｎｃ－ＵＳＰ４７－２：１、ＲＢＭ２６－ＡＳ１：１、ＭＩＲ１８１Ａ２ＨＧ：１、ＴＴＣ２１Ｂ－ＡＳ１：２、ＬＥＦ１－ＡＳ１：１、ｌｎｃ－ＳＬＣ３５Ｅ３－８：１、ｌｎｃ－ＺＣＣＨＣ１３－４：１、ｌｎｃ－ＮＥＭＦ－１：４、ＴＣＯＮＳ＿０００１１９９４、ｌｎｃ－ＥＶＸ１－１５：１、ｌｎｃ－ＲＥＣ８－２：１、ＯＩＰ５－ＡＳ１：３６、ＭＹＬＫ－ＡＳ１：１３、ｌｎｃ－ＰＣＰ４Ｌ１－３：２、ｌｎｃ－ＣＧＲＥＦ１－２：１、ＺＣ３Ｈ１２Ｂ－１１：１、ＰＳＭＢ８－ＡＳ１：１４、ｌｎｃ－ＳＴＸ１０－２：１、ｌｎｃ－ＴＣＦＬ５－６：１、ｌｎｃ－ＵＱＣＣ３－２：１、ｌｎｃ－ＺＮＦ５１６－１４：１、ｌｎｃ－ＰＤＧＦＡ－６：２、ｌｎｃ－ＦＯＸＤ４Ｌ５－１６：１、ｌｎｃ－ＳＡＭＤ１１－１２：４、ｌｎｃ－ＡＤＡＤ１－３：１、ｌｎｃ－ＳＬＣ３５Ｅ３－８：２、ｌｎｃ－ＮＩＤ１－４：４、ＦＴＸ：１９、ＴＣＯＮＳ＿０００１７３７２、ｌｎｃ－ＧＲＡＰ－１：２）（「ｌｎｃＲＮＡシグナチャー２」）から選択される少なくとも１つのｌｎｃＲＮＡを含むか、またはそれからなる、請求項１に記載の方法。 The lncRNA signature spans 54 lncRNAs (lnc-ANAPC11-2:8, lnc-CLLU1-2:6, lnc-KLHL36-2:2, lnc-LRRC10-1:1, lnc-RMDN2-3:24, lnc- SMN2-4:2, lnc-SPRYD3-1:17, lnc-USP47-2:1, lnc-ZC3H12B-1:5, TCONS_00019798, TSPOAP1-AS1:39, TCONS_00035093, lnc-OCM-3:4, lnc- KIF14-1:2, PCBP1-AS1:302, lnc-CA6-8:1, NEAT1:22, lnc-CA6-8:2, STARD7-AS1:5, lnc-IL31RA-1:1, lnc-ANKRD36- 1:4, lnc-ATP6AP2-13:1, lnc-SOCS6-10:1, lnc-CDIPT-2:1, lnc-USP47-2:1, RBM26-AS1:1, MIR181A2HG:1, TTC21B-AS1: 2, LEF1-AS1:1, lnc-SLC35E3-8:1, lnc-ZCCHC13-4:1, lnc-NEMF-1:4, TCONS_00011994, lnc-EVX1-15:1, lnc-REC8-2:1, OIP5-AS1:36, MYLK-AS1:13, lnc-PCP4L1-3:2, lnc-CGREF1-2:1, ZC3H12B-11:1, PSMB8-AS1:14, lnc-STX10-2:1, lnc- TCFL5-6:1, lnc-UQCC3-2:1, lnc-ZNF516-14:1, lnc-PDGFA-6:2, lnc-FOXD4L5-16:1, lnc-SAMD11-12:4, lnc-ADAD1- 3:1, lnc-SLC35E3-8:2, lnc-NID1-4:4, FTX:19, TCONS_00017372, lnc-GRAP-1:2) ("lncRNA signature 2") 2. The method of claim 1, comprising or consisting of. ｌｎｃＲＮＡシグナチャーが、６つのｌｎｃＲＮＡ（ＴＣＯＮＳ＿０００４５３６４、ＴＣＯＮＳ＿０００３５０２３、ＴＣＯＮＳ＿０００３５０９１、ＴＣＯＮＳ＿０００３５０２２、ＴＣＯＮＳ＿０００３５０９２、ＴＣＯＮＳ＿０００３５０９３）（「ｌｎｃＲＮＡシグナチャー６」）から選択される少なくとも１つのｌｎｃＲＮＡを含むか、またはそれからなる、請求項１に記載の方法。 2. The method of claim 1, wherein the lncRNA signature is selected from six lncRNAs (TCONS_00045364, TCONS_00035023, TCONS_00035091, TCONS_00035022, TCONS_00035092, TCONS_00035093) ("lncRNA signature 6"), or at least one lncRNA of claim 1, or consisting of . 工程（ａ）において、ｌｎｃＲＮＡの発現レベルが、神経認知検査、神経イメージング法および／またはＣＳＦバイオマーカーなどの認知障害の検出にとって好適な別のバイオマーカーと組み合わせて検出される、請求項１から３のいずれか一項に記載の方法。 4. Claims 1 to 3, wherein in step ( a ) the lncRNA expression level is detected in combination with another biomarker suitable for detection of cognitive impairment such as neurocognitive tests, neuroimaging methods and/or CSF biomarkers. The method according to any one of . 認知機能の喪失もしくは障害または認知症に罹患する対象における認知障害の発症または進行をモニタリングするための請求項１から４のいずれか一項に記載の方法であって、工程（ａ）および（ｂ）、ならびに
（ｃ）前記同定された認知障害に従って治療的処置を設計すること
を含む、前記方法。 5. The method of any one of claims 1-4 for monitoring the onset or progression of cognitive impairment in a subject suffering from cognitive loss or impairment or dementia, comprising steps (a) and (b) ), and ( c ) designing a therapeutic treatment according to the identified cognitive impairment. 生体試料が、血液、血漿、血清、唾液、涙液、尿または脳脊髄液から選択される、請求項１から５のいずれか一項に記載の方法。 6. A method according to any one of claims 1 to 5 , wherein the biological sample is selected from blood, plasma, serum, saliva, tears, urine or cerebrospinal fluid. 認知障害もしくは任意の認知症型が診断される（健康な対照に対する差異）か、または特定の型の認知症が、限定されるものではないが、アルツハイマー病（ＡＤ）、ＡＤ型の軽度認知障害（ＭＣＩ）、前頭側頭型認知症（ＦＴＤ）およびＦＴＤ型のＭＣＩ、レヴィー小体型認知症（ＤＬＢ）およびＤＬＢ型のＭＣＩ、パーキンソン病型認知症（ＰＤＤ）およびＰＤＤ型のＭＣＩ、血管性認知症、進行性核上麻痺（ＰＳＰ）、および大脳皮質基底核変性症（ＣＢＤ）を含む他の型の認知症に対して診断される、請求項１から６のいずれか一項に記載の方法。 Cognitive impairment or any type of dementia is diagnosed (difference to healthy controls), or a specific type of dementia, including but not limited to Alzheimer's disease (AD), AD type mild cognitive impairment (MCI), frontotemporal dementia (FTD) and MCI of type FTD, dementia with Lewy bodies (DLB) and MCI of type DLB, dementia of Parkinson's disease (PDD) and MCI of type PDD, vascular cognition 7. The method of any one of claims 1 to 6 , wherein the patient is diagnosed for other forms of dementia, including dementia, progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD). . 限定されるものではないが、ＡＤを含む認知障害を診断および／またはモニタリングするためのキットであって、５４のｌｎｃＲＮＡ（ｌｎｃ－ＡＮＡＰＣ１１－２：８、ｌｎｃ－ＣＬＬＵ１－２：６、ｌｎｃ－ＫＬＨＬ３６－２：２、ｌｎｃ－ＬＲＲＣ１０－１：１、ｌｎｃ－ＲＭＤＮ２－３：２４、ｌｎｃ－ＳＭＮ２－４：２、ｌｎｃ－ＳＰＲＹＤ３－１：１７、ｌｎｃ－ＵＳＰ４７－２：１、ｌｎｃ－ＺＣ３Ｈ１２Ｂ－１：５、ＴＣＯＮＳ＿０００１９７９８、ＴＳＰＯＡＰ１－ＡＳ１：３９、ＴＣＯＮＳ＿０００３５０９３、ｌｎｃ－ＯＣＭ－３：４、ｌｎｃ－ＫＩＦ１４－１：２、ＰＣＢＰ１－ＡＳ１：３０２、ｌｎｃ－ＣＡ６－８：１、ＮＥＡＴ１：２２、ｌｎｃ－ＣＡ６－８：２、ＳＴＡＲＤ７－ＡＳ１：５、ｌｎｃ－ＩＬ３１ＲＡ－１：１、ｌｎｃ－ＡＮＫＲＤ３６－１：４、ｌｎｃ－ＡＴＰ６ＡＰ２－１３：１、ｌｎｃ－ＳＯＣＳ６－１０：１、ｌｎｃ－ＣＤＩＰＴ－２：１、ｌｎｃ－ＵＳＰ４７－２：１、ＲＢＭ２６－ＡＳ１：１、ＭＩＲ１８１Ａ２ＨＧ：１、ＴＴＣ２１Ｂ－ＡＳ１：２、ＬＥＦ１－ＡＳ１：１、ｌｎｃ－ＳＬＣ３５Ｅ３－８：１、ｌｎｃ－ＺＣＣＨＣ１３－４：１、ｌｎｃ－ＮＥＭＦ－１：４、ＴＣＯＮＳ＿０００１１９９４、ｌｎｃ－ＥＶＸ１－１５：１、ｌｎｃ－ＲＥＣ８－２：１、ＯＩＰ５－ＡＳ１：３６、ＭＹＬＫ－ＡＳ１：１３、ｌｎｃ－ＰＣＰ４Ｌ１－３：２、ｌｎｃ－ＣＧＲＥＦ１－２：１、ＺＣ３Ｈ１２Ｂ－１１：１、ＰＳＭＢ８－ＡＳ１：１４、ｌｎｃ－ＳＴＸ１０－２：１、ｌｎｃ－ＴＣＦＬ５－６：１、ｌｎｃ－ＵＱＣＣ３－２：１、ｌｎｃ－ＺＮＦ５１６－１４：１、ｌｎｃ－ＰＤＧＦＡ－６：２、ｌｎｃ－ＦＯＸＤ４Ｌ５－１６：１、ｌｎｃ－ＳＡＭＤ１１－１２：４、ｌｎｃ－ＡＤＡＤ１－３：１、ｌｎｃ－ＳＬＣ３５Ｅ３－８：２、ｌｎｃ－ＮＩＤ１－４：４、ＦＴＸ：１９、ＴＣＯＮＳ＿０００１７３７２、ｌｎｃ－ＧＲＡＰ－１：２）（「ｌｎｃＲＮＡシグナチャー２」）から選択される少なくとも１つのｌｎｃＲＮＡを含むか、またはそれからなるｌｎｃＲＮＡ発現プロファイルの決定のための少なくとも１つの試薬を含む、キット。 A kit for diagnosing and/or monitoring cognitive disorders, including but not limited to AD, comprising 54 lncRNAs (lnc-ANAPC11-2:8, lnc-CLLU1-2:6, lnc-KLHL36 -2:2, lnc-LRRC10-1:1, lnc-RMDN2-3:24, lnc-SMN2-4:2, lnc-SPRYD3-1:17, lnc-USP47-2:1, lnc-ZC3H12B-1 :5, TCONS_00019798, TSPOAP1-AS1:39, TCONS_00035093, lnc-OCM-3:4, lnc-KIF14-1:2, PCBP1-AS1:302, lnc-CA6-8:1, NEAT1:22, lnc-CA6 -8:2, STARD7-AS1:5, lnc-IL31RA-1:1, lnc-ANKRD36-1:4, lnc-ATP6AP2-13:1, lnc-SOCS6-10:1, lnc-CDIPT-2:1 , lnc-USP47-2:1, RBM26-AS1:1, MIR181A2HG:1, TTC21B-AS1:2, LEF1-AS1:1, lnc-SLC35E3-8:1, lnc-ZCCHC13-4:1, lnc-NEMF -1:4, TCONS_00011994, lnc-EVX1-15:1, lnc-REC8-2:1, OIP5-AS1:36, MYLK-AS1:13, lnc-PCP4L1-3:2, lnc-CGREF1-2:1 , ZC3H12B-11:1, PSMB8-AS1:14, lnc-STX10-2:1, lnc-TCFL5-6:1, lnc-UQCC3-2:1, lnc-ZNF516-14:1, lnc-PDGFA-6 :2, lnc-FOXD4L5-16:1, lnc-SAMD11-12:4, lnc-ADAD1-3:1, lnc-SLC35E3-8:2, lnc-NID1-4:4, FTX:19, TCONS_00017372, lnc -GRAP-1:2) (“lncRNA signature 2”), comprising at least one reagent for the determination of a lncRNA expression profile, comprising or consisting of at least one lncRNA selected from: 少なくとも１つの試薬が、目的のｌｎｃＲＮＡと相補的な特異的オリゴヌクレオチドを含む、請求項８に記載のキット。 9. The kit of Claim 8 , wherein at least one reagent comprises a specific oligonucleotide complementary to the lncRNA of interest. ６８のｌｎｃＲＮＡ（ＴＣＯＮＳ＿０００５０５３９、ＴＣＯＮＳ＿０００６２５５５、ＴＣＯＮＳ＿０００２４９１６、ＴＣＯＮＳ＿０００５９１９８、ＴＣＯＮＳ＿０００６６４６２、ＴＣＯＮＳ＿０００３３６５３、ＬＩＮＣ－ＰＩＮＴ：１６、ｌｎｃ－ＡＴＰ６Ｖ１Ｃ１－１２：１、ｌｎｃ－ＧＡＢＢＲ１－１：２、ｌｎｃ－ＰＭＭ２－６：２、ＭＡＬＡＴ１：２３、ＭＡＬＡＴ１：４８、ｌｎｃ－ＬＴＢＰ３－２：６、ｌｎｃ－ＬＴＢＰ３－２：３、ｌｎｃ－ＡＮＡＰＣ１１－２：８、ｌｎｃ－ＣＬＬＵ１－２：６、ｌｎｃ－ＫＬＨＬ３６－２：２、ｌｎｃ－ＬＲＲＣ１０－１：１、ｌｎｃ－ＲＭＤＮ２－３：２４、ｌｎｃ－ＳＭＮ２－４：２、ｌｎｃ－ＳＰＲＹＤ３－１：１７、ｌｎｃ－ＵＳＰ４７－２：１、ｌｎｃ－ＺＣ３Ｈ１２Ｂ－１：５、ＴＣＯＮＳ＿０００１９７９８、ＴＳＰＯＡＰ１－ＡＳ１：３９、ＴＣＯＮＳ＿０００３５０９３、ｌｎｃ－ＯＣＭ－３：４、ｌｎｃ－ＫＩＦ１４－１：２、ＰＣＢＰ１－ＡＳ１：３０２、ｌｎｃ－ＣＡ６－８：１、ＮＥＡＴ１：２２、ｌｎｃ－ＣＡ６－８：２、ＳＴＡＲＤ７－ＡＳ１：５、ｌｎｃ－ＩＬ３１ＲＡ－１：１、ｌｎｃ－ＡＮＫＲＤ３６－１：４、ｌｎｃ－ＡＴＰ６ＡＰ２－１３：１、ｌｎｃ－ＳＯＣＳ６－１０：１、ｌｎｃ－ＣＤＩＰＴ－２：１、ｌｎｃ－ＵＳＰ４７－２：１、ＲＢＭ２６－ＡＳ１：１、ＭＩＲ１８１Ａ２ＨＧ：１、ＴＴＣ２１Ｂ－ＡＳ１：２、ＬＥＦ１－ＡＳ１：１、ｌｎｃ－ＳＬＣ３５Ｅ３－８：１、ｌｎｃ－ＺＣＣＨＣ１３－４：１、ｌｎｃ－ＮＥＭＦ－１：４、ＴＣＯＮＳ＿０００１１９９４、ｌｎｃ－ＥＶＸ１－１５：１、ｌｎｃ－ＲＥＣ８－２：１、ＯＩＰ５－ＡＳ１：３６、ＭＹＬＫ－ＡＳ１：１３、ｌｎｃ－ＰＣＰ４Ｌ１－３：２、ｌｎｃ－ＣＧＲＥＦ１－２：１、ＺＣ３Ｈ１２Ｂ－１１：１、ＰＳＭＢ８－ＡＳ１：１４、ｌｎｃ－ＳＴＸ１０－２：１、ｌｎｃ－ＴＣＦＬ５－６：１、ｌｎｃ－ＵＱＣＣ３－２：１、ｌｎｃ－ＺＮＦ５１６－１４：１、ｌｎｃ－ＰＤＧＦＡ－６：２、ｌｎｃ－ＦＯＸＤ４Ｌ５－１６：１、ｌｎｃ－ＳＡＭＤ１１－１２：４、ｌｎｃ－ＡＤＡＤ１－３：１、ｌｎｃ－ＳＬＣ３５Ｅ３－８：２、ｌｎｃ－ＮＩＤ１－４：４、ＦＴＸ：１９、ＴＣＯＮＳ＿０００１７３７２、ｌｎｃ－ＧＲＡＰ－１：２）（「ｌｎｃＲＮＡシグナチャー１」）から選択される少なくとも１つのｌｎｃＲＮＡに特異的な核酸を含む、次世代シーケンシングのための標的シーケンシングパネル。 ６８のｌｎｃＲＮＡ（ＴＣＯＮＳ＿０００５０５３９、ＴＣＯＮＳ＿０００６２５５５、ＴＣＯＮＳ＿０００２４９１６、ＴＣＯＮＳ＿０００５９１９８、ＴＣＯＮＳ＿０００６６４６２、ＴＣＯＮＳ＿０００３３６５３、ＬＩＮＣ－ＰＩＮＴ：１６、ｌｎｃ－ＡＴＰ６Ｖ１Ｃ１－１２：１、ｌｎｃ－ＧＡＢＢＲ１－１：２、ｌｎｃ－ＰＭＭ２－６：２、ＭＡＬＡＴ１：２３、 MALAT1:48, lnc-LTBP3-2:6, lnc-LTBP3-2:3, lnc-ANAPC11-2:8, lnc-CLLU1-2:6, lnc-KLHL36-2:2, lnc-LRRC10-1: 1, lnc-RMDN2-3:24, lnc-SMN2-4:2, lnc-SPRYD3-1:17, lnc-USP47-2:1, lnc-ZC3H12B-1:5, TCONS_00019798, TSPOAP1-AS1:39, TCONS_00035093, lnc-OCM-3:4, lnc-KIF14-1:2, PCBP1-AS1:302, lnc-CA6-8:1, NEAT1:22, lnc-CA6-8:2, STARD7-AS1:5, lnc-IL31RA-1:1, lnc-ANKRD36-1:4, lnc-ATP6AP2-13:1, lnc-SOCS6-10:1, lnc-CDIPT-2:1, lnc-USP47-2:1, RBM26- AS1:1, MIR181A2HG:1, TTC21B-AS1:2, LEF1-AS1:1, lnc-SLC35E3-8:1, lnc-ZCCHC13-4:1, lnc-NEMF-1:4, TCONS_00011994, lnc-EVX1- 15:1, lnc-REC8-2:1, OIP5-AS1:36, MYLK-AS1:13, lnc-PCP4L1-3:2, lnc-CGREF1-2:1, ZC3H12B-11:1, PSMB8-AS1: 14, lnc-STX10-2:1, lnc-TCFL5-6:1, lnc-UQCC3-2:1, lnc-ZNF516-14:1, lnc-PDGFA-6:2, lnc-FOXD4L5-16:1, lnc-SAMD11-12:4, lnc-ADAD1-3:1, lnc-SLC35E3-8:2, lnc-NID1-4:4, FTX:19, TCONS_00017372, lnc-GRAP-1:2) ("lncRNA signature 1") at least one lncRNA selected from A targeted sequencing panel for next-generation sequencing comprising nucleic acids specific for . 軽度認知障害または認知障害を有するか、または発症するリスクがある対象における、脳疾患、特に、軽度認知障害（ＭＣＩ）およびアルツハイマー病または別の認知障害の処置における使用のためのｌｎｃＲＮＡを含む組成物であって、処置が、対象に、脳および／または末梢中のｌｎｃＲＮＡの発現をモジュレートする（誘導する、または阻害する）有効量の医薬品を投与することを含み、ｌｎｃＲＮＡが、以下のｌｎｃＲＮＡシグナチャー：
（ｉ）２１のｌｎｃＲＮＡ（ＴＣＯＮＳ＿０００５０５３９、ＴＣＯＮＳ＿０００６２５５５、ＴＣＯＮＳ＿０００２４９１６、ＴＣＯＮＳ＿０００５９１９８、ＴＣＯＮＳ＿０００６６４６２、ＴＣＯＮＳ＿０００３３６５３、ＴＣＯＮＳ＿０００４０８７８、ＴＣＯＮＳ＿０００００６３４、ＴＣＯＮＳ＿０００５０１７８、ＴＣＯＮＳ＿０００５５４９６、ＴＣＯＮＳ＿０００３３７３６、ＴＣＯＮＳ＿０００２３３０９、ＴＣＯＮＳ＿０００２７７６５、ＴＣＯＮＳ＿０００６２６０２、ＴＣＯＮＳ＿００００５３２５、ＴＣＯＮＳ＿０００１１９７４、ＴＣＯＮＳ＿０００２３２４０、ＴＣＯＮＳ＿０００２３４０１、ＴＣＯＮＳ＿０００６６３５８、ＴＣＯＮＳ＿０００６２３０６、ＴＣＯＮＳ＿０００２７４３８）（「ｌｎｃＲＮＡシグナチャー１２」）；
（ｉｉ）１０のｌｎｃＲＮＡ（ＬＩＮＣ－ＰＩＮＴ：１６、ｌｎｃ－ＡＴＰ６Ｖ１Ｃ１－１２：１、ｌｎｃ－ＧＡＢＢＲ１－１：２、ｌｎｃ－ＰＭＭ２－６：２、ＭＡＬＡＴ１：２３、ＭＡＬＡＴ１：４８、ｌｎｃ－ＬＴＢＰ３－２：６、ｌｎｃ－ＬＴＢＰ３－２：３、ＭＡＬＡＴ１：１１、ｌｎｃ－ＬＴＢＰ３－２：２）（「ｌｎｃＲＮＡシグナチャー１３」）；
（ｉｉｉ）１７のｌｎｃＲＮＡ（ＴＣＯＮＳ＿０００３５０２２、ＴＣＯＮＳ＿０００３５０２３、ＴＣＯＮＳ＿０００３５０９４、ＴＣＯＮＳ＿０００３５０９３、ＴＣＯＮＳ＿０００３５０２１、ＴＣＯＮＳ＿０００３５０９０、ＴＣＯＮＳ＿０００３５０２４、ＴＣＯＮＳ＿０００３５０９１、ＴＣＯＮＳ＿０００１２０５９、ＴＣＯＮＳ＿０００３５０９２、ＴＣＯＮＳ＿０００１２０６０、ＴＣＯＮＳ＿０００５００１４、ｌｎｃ－ＥＮＣ１－５：１、ｌｎｃ－ＳＮＡＰ２５－３：１、ｌｎｃ－ＨＭＧＡ１－２：４、ＰＥＧ３－ＡＳ１：１、ｌｎｃ－ＵＮＣ８０－１：１）（「ｌｎｃＲＮＡシグナチャー１４」）；
（ｉｖ）１７のｌｎｃＲＮＡ（ｌｎｃ－ＮＥＫ６－２：１、ｌｎｃ－ＰＭＭ２－６：４、ＵＧＤＨ－ＡＳ１：１０、ｌｎｃ－ＲＭＤＮ２－３：２４、ｌｎｃ－ＥＩＦ１ＡＤ－１：１、ｌｎｃ－ＦＡＮＣＬ－４：１、ｌｎｃ－ＦＡＡＰ１００－２：１、ＴＣＯＮＳ＿０００１１９７４、ｌｎｃ－ＦＥＭ１Ｂ－４：１、ｌｎｃ－ＧＮＡ１４－３：１、ｌｎｃ－ＰＩＮＫ１－２：１、ｌｎｃ－ＰＲＳＳ２７－４：２４、ｌｎｃ－ＳＬＣ２５Ａ３－７：１、ｌｎｃ－ＦＥＭ１Ｂ－４：１、ＮＯＲＡＤ：２、ＮＯＲＡＤ：８、ＣＡＣＴＩＮ－ＡＳ１：５）（「ｌｎｃＲＮＡシグナチャー４２」）の１つから選択される少なくとも１つのｌｎｃＲＮＡである、組成物。 Compositions comprising lncRNAs for use in the treatment of brain disorders, particularly mild cognitive impairment (MCI) and Alzheimer's disease or another cognitive disorder, in subjects having or at risk of developing mild cognitive impairment or cognitive impairment wherein treatment comprises administering to the subject an effective amount of a pharmaceutical agent that modulates (induces or inhibits) expression of a lncRNA in the brain and/or periphery, wherein the lncRNA has the following lncRNA signature :
（ｉ）２１のｌｎｃＲＮＡ（ＴＣＯＮＳ＿０００５０５３９、ＴＣＯＮＳ＿０００６２５５５、ＴＣＯＮＳ＿０００２４９１６、ＴＣＯＮＳ＿０００５９１９８、ＴＣＯＮＳ＿０００６６４６２、ＴＣＯＮＳ＿０００３３６５３、ＴＣＯＮＳ＿０００４０８７８、ＴＣＯＮＳ＿０００００６３４、ＴＣＯＮＳ＿０００５０１７８、ＴＣＯＮＳ＿０００５５４９６、ＴＣＯＮＳ＿０００３３７３６、ＴＣＯＮＳ＿０００２３３０９、ＴＣＯＮＳ＿０００２７７６５、ＴＣＯＮＳ＿０００６２６０２、ＴＣＯＮＳ＿００００５３２５、ＴＣＯＮＳ＿０００１１９７４、ＴＣＯＮＳ＿０００２３２４０、ＴＣＯＮＳ＿０００２３４０１、ＴＣＯＮＳ＿０００６６３５８、ＴＣＯＮＳ＿０００６２３０６、ＴＣＯＮＳ＿０００２７４３８）（ "lncRNA signature 12");
(ii) 10 lncRNAs (LINC-PINT:16, lnc-ATP6V1C1-12:1, lnc-GABBR1-1:2, lnc-PMM2-6:2, MALAT1:23, MALAT1:48, lnc-LTBP3-2 :6, lnc-LTBP3-2:3, MALAT1:11, lnc-LTBP3-2:2) (“lncRNA signature 13”);
（ｉｉｉ）１７のｌｎｃＲＮＡ（ＴＣＯＮＳ＿０００３５０２２、ＴＣＯＮＳ＿０００３５０２３、ＴＣＯＮＳ＿０００３５０９４、ＴＣＯＮＳ＿０００３５０９３、ＴＣＯＮＳ＿０００３５０２１、ＴＣＯＮＳ＿０００３５０９０、ＴＣＯＮＳ＿０００３５０２４、ＴＣＯＮＳ＿０００３５０９１、ＴＣＯＮＳ＿０００１２０５９、ＴＣＯＮＳ＿０００３５０９２、ＴＣＯＮＳ＿０００１２０６０、ＴＣＯＮＳ＿０００５００１４、ｌｎｃ－ＥＮＣ１－５：１、ｌｎｃ－ＳＮＡＰ２５－３：１、ｌｎｃ－ＨＭＧＡ１ -2:4, PEG3-AS1:1, lnc-UNC80-1:1) (“lncRNA signature 14”);
(iv) 17 lncRNAs (lnc-NEK6-2:1, lnc-PMM2-6:4, UGDH-AS1:10, lnc-RMDN2-3:24, lnc-EIF1AD-1:1, lnc-FANCL-4 :1, lnc-FAAP100-2:1, TCONS_00011974, lnc-FEM1B-4:1, lnc-GNA14-3:1, lnc-PINK1-2:1, lnc-PRSS27-4:24, lnc-SLC25A3-7 : 1, lnc-FEM1B-4:1, NORAD:2, NORAD:8, CACTIN -AS1:5) (“lncRNA signature 42”).
JP2021512725A 2018-09-05 2019-09-05 Long non-coding RNA (lncRNA) for the diagnosis and treatment of brain disorders, especially cognitive disorders Pending JP2022501016A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2024021135A JP2024073440A (en) 2018-09-05 2024-02-15 Long non-coding RNA (lncRNA) for the diagnosis and treatment of brain disorders, particularly cognitive disorders

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201862727210P 2018-09-05 2018-09-05
US62/727,210 2018-09-05
PCT/EP2019/073775 WO2020049135A1 (en) 2018-09-05 2019-09-05 Long non-coding rnas (lncrnas) for the diagnosis and therapeutics of brain disorders, in particular cognitive disorders

Related Child Applications (1)

Application Number Title Priority Date Filing Date
JP2024021135A Division JP2024073440A (en) 2018-09-05 2024-02-15 Long non-coding RNA (lncRNA) for the diagnosis and treatment of brain disorders, particularly cognitive disorders

Publications (2)

Publication Number Publication Date
JP2022501016A JP2022501016A (en) 2022-01-06
JPWO2020049135A5 true JPWO2020049135A5 (en) 2022-09-12

Family

ID=67902523

Family Applications (2)

Application Number Title Priority Date Filing Date
JP2021512725A Pending JP2022501016A (en) 2018-09-05 2019-09-05 Long non-coding RNA (lncRNA) for the diagnosis and treatment of brain disorders, especially cognitive disorders
JP2024021135A Pending JP2024073440A (en) 2018-09-05 2024-02-15 Long non-coding RNA (lncRNA) for the diagnosis and treatment of brain disorders, particularly cognitive disorders

Family Applications After (1)

Application Number Title Priority Date Filing Date
JP2024021135A Pending JP2024073440A (en) 2018-09-05 2024-02-15 Long non-coding RNA (lncRNA) for the diagnosis and treatment of brain disorders, particularly cognitive disorders

Country Status (5)

Country Link
US (1) US20210269881A1 (en)
EP (1) EP3847279B1 (en)
JP (2) JP2022501016A (en)
CN (1) CN113286895A (en)
WO (1) WO2020049135A1 (en)

Families Citing this family (30)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR102392236B1 (en) * 2016-05-18 2022-05-03 보이저 테라퓨틱스, 인크. Regulatory Polynucleotides
WO2019048500A1 (en) 2017-09-05 2019-03-14 Amoneta Diagnostics Non-coding rnas (ncrna) for the diagnosis of cognitive disorders
CN110564833A (en) * 2019-08-23 2019-12-13 杭州迪安医学检验中心有限公司 Kit for FFPE sample DNA quality control and detection method
CN111518906B (en) * 2020-05-12 2022-07-05 广州医科大学附属第五医院 Application of lncRNA01622 in recurrence prediction and treatment of hepatocellular carcinoma
CN111690739B (en) * 2020-07-31 2022-09-16 上海市精神卫生中心（上海市心理咨询培训中心） MCI diagnostic marker, MCI diagnostic kit and corresponding detection method
CN112143801B (en) * 2020-10-13 2022-07-22 南京鸿瑞杰生物医疗科技有限公司 Biomarker for early diagnosis of Alzheimer's disease
CN112575076A (en) * 2020-11-02 2021-03-30 深圳恒生医院 LncRNA marker for detecting and evaluating early spontaneous abortion and product using LncRNA marker
CN112795655B (en) * 2021-02-08 2021-08-24 青岛市中心医院 Colorectal cancer diagnosis marker and diagnosis kit thereof
CN113262304B (en) * 2021-04-26 2022-12-06 暨南大学 Application of miR-4435-2HG and/or GDAP1 gene inhibitor in preparation of medicine for treating AML
CN113862366A (en) * 2021-10-26 2021-12-31 山东师范大学 Biomarker for liver cancer diagnosis and diagnosis kit thereof
CN113981091A (en) * 2021-11-24 2022-01-28 中南大学湘雅医院 WTAP as nasopharyngeal carcinoma prognosis prediction marker, detection primer and kit
CN114236123B (en) * 2021-12-13 2024-04-19 深圳华大基因股份有限公司 Application of marker in predicting gestational diabetes risk
CN114214290B (en) * 2021-12-27 2023-12-01 吉林大学 Recombinant adenovirus ADV-lncRNA Gm44275 and construction method and application thereof
CN114480390B (en) * 2022-01-26 2023-10-20 广州市红十字会医院（暨南大学医学院附属广州红十字会医院） siRNA, siRNA plasmid and lentivirus for targeted inhibition of ZNF22 gene expression as well as construction method and application thereof
WO2023206347A1 (en) * 2022-04-29 2023-11-02 苏州瀛创生物科技有限公司 Ddit4l spliced product as diagnostic marker for alzheimer's disease
US11866707B2 (en) 2022-05-18 2024-01-09 Zhejiang Cancer Hospital Use of non-coding RNA SNHG17 as biomarker and therapeutic target
CN114717242A (en) * 2022-05-20 2022-07-08 中国医学科学院肿瘤医院 Application of LOC107984813 in diagnosis, prognosis prediction and cancer treatment
CN114886910B (en) * 2022-06-21 2023-09-22 上海市同仁医院 Application of LINC00938 in nerve cell apoptosis
CN116808216A (en) * 2022-07-06 2023-09-29 四川大学 Application of ALPK1 gene as control target point of central nervous system diseases caused by cerebral ischemia
CN116064557B (en) * 2022-09-15 2024-06-04 华中农业大学 Application of preparation for activating OGFOD gene expression of pig in preparation of medicine for resisting pseudorabies virus infection of pig
CN116103410A (en) * 2023-02-09 2023-05-12 新疆畜牧科学院生物技术研究所（新疆畜牧科学院中国-澳大利亚绵羊育种研究中心） Breeding method of Babuk sheep and Indel molecular marker of wool color character of Babuk sheep
CN116327795A (en) * 2023-02-22 2023-06-27 深圳市第二人民医院(深圳市转化医学研究院) Application of LINC01089 in preparation of medicines for treating cancers
CN116287277A (en) * 2023-04-24 2023-06-23 上海生物制品研究所有限责任公司 Biomarker of cytidine deaminase activity and application thereof
CN116637123B (en) * 2023-06-07 2024-02-13 上海市东方医院（同济大学附属东方医院） Application of reagent for knocking down or down expression of C15orf39 gene in preparation of medicines for treating gastric cancer
CN116926189B (en) * 2023-09-12 2023-12-01 上海益诺思生物技术股份有限公司 Application of exosome lncRNA in detection of drug-induced myocardial injury
CN117051102B (en) * 2023-10-12 2024-01-26 上海爱谱蒂康生物科技有限公司 Application of biomarker combination in preparation of products for predicting parkinsonism
CN117653653A (en) * 2023-10-19 2024-03-08 复旦大学附属肿瘤医院 Small molecule nucleic acid medicine for intervening cancer specific LINC01419 and application thereof in liver cancer targeted therapy
CN117701563A (en) * 2023-11-23 2024-03-15 西南医科大学 Sequence optimization of small molecule RNA candidate drug and application thereof in treatment of diabetic cardiomyopathy
CN117385024B (en) * 2023-11-29 2024-04-19 梅州市人民医院(梅州市医学科学院) LncRNA marker and application thereof in preparation of products for diagnosing, screening or evaluating acute coronary syndromes
CN117393044B (en) * 2023-12-11 2024-02-27 四川大学华西医院 Kit for early screening of mild cognitive impairment and diagnosis system

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6407132B1 (en) 1997-07-25 2002-06-18 James Black Foundation Limited Substituted imidazole derivatives and their use as histamine H3 receptor ligands
WO2005071059A2 (en) * 2004-01-27 2005-08-04 Compugen Ltd. Methods of identifying putative gene products by interspecies sequence comparison and biomolecular sequences uncovered thereby
FR2882056B1 (en) 2005-02-15 2007-06-01 Centre Nat Rech Scient UNSATURATED BOROCARBON DIPYRROMETHENES-BORE
US9377472B2 (en) 2012-04-30 2016-06-28 Amoneta Diagnostics Biological complex specific for Alzheimer's disease detection in vitro and use thereof
WO2015031958A1 (en) * 2013-09-06 2015-03-12 Garvan Institute Of Medical Research Regulatory molecules

Similar Documents

Publication Publication Date Title
JPWO2020049135A5 (en)
Zetterberg et al. Cerebrospinal fluid markers for prediction of Alzheimer's disease
Sudduth et al. Neuroinflammatory phenotype in early Alzheimer's disease
Craig-Schapiro et al. YKL-40: a novel prognostic fluid biomarker for preclinical Alzheimer's disease
Dukic et al. The role of human kallikrein 6, clusterin and adiponectin as potential blood biomarkers of dementia
JP6228302B2 (en) Blood-based screening to detect neurological diseases in primary care settings
JP2020536503A5 (en)
JP2012523009A5 (en)
Henchcliffe et al. Biomarkers of Parkinson's disease and Dementia with Lewy bodies
JP2008544225A (en) Methods and compositions for diagnosis of neurological disorders in body fluids
JP2009540309A (en) In vitro multiparameter measurement method for diagnosis and early diagnosis of neurodegenerative disorders
ES2762919T3 (en) Method for in vitro diagnosis of Lewy body dementia using alpha-synuclein gene transcripts
Rosén et al. Cerebrospinal fluid biomarkers in cardiac arrest survivors
JP5295101B2 (en) In vitro method for providing evaluation index of progress and prognosis of neurodegenerative disease
Khalil et al. Impaired peripheral endothelial microvascular responsiveness in Alzheimer's disease
Kim et al. Does delayed facial involvement implicate a pattern of “descending reversible paralysis” in Fisher syndrome?
Stankovic et al. Laboratory‐supported multiple system atrophy beyond autonomic function testing and imaging: A systematic review by the MoDiMSA study group
US20220326259A1 (en) In vitro diagnostic method for alzheimer's disease based on the albumin redox level in the cerebrospinal fluid
Peles et al. Accuracy of the brief cognitive screening battery for diagnosing Alzheimer's disease defined by cerebrospinal fluid biomarkers and AT (N) classification: a case-control study
Mizrahi et al. Serum albumin levels predict cognitive impairment in elderly hip fracture patients
US20140273032A1 (en) Compositions and methods for diagnosis of schizophrenia
CN113167800A (en) Method for the differential diagnosis of neurodegenerative diseases in a subject
CN112567248A (en) Method for the differential diagnosis of neurodegenerative diseases in a subject
TWI452140B (en) Compositions and methods for diagnosis of schizophrenia
Robles-Cedeño et al. Rapidly progressive dementia with false-positive PCR Tropheryma whipplei in CSF. A case of Hashimoto's encephalopathy