IPC분류정보
국가/구분 |
United States(US) Patent
공개
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국제특허분류(IPC7판) |
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출원번호 |
16096219
(2017-04-25)
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공개번호 |
20190136320
(2019-05-09)
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우선권정보 |
PL-PL416956 (2016-04-25); IB-PCT/IB2016/052440 (2016-04-29) |
국제출원번호 |
PCT/EP2017/059800
(2017-04-25)
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발명자
/ 주소 |
- Wojda, Urszula
- Laskowska-Kaszub, Katarzyna
- Gabryelewicz, Tomasz
- Kuznicki, Jacek
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출원인 / 주소 |
- Instytut Biologii Doswiadczalnej im. Marcelego Nenckiego Polska Akademia Nauk
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인용정보 |
피인용 횟수 :
0 인용 특허 :
0 |
초록
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The present invention relates to panels of biomarker microRNAs for use in methods of diagnosing Alzheimer's disease and related diseases and conditions in a subject. The methods involve assessing the level of said biomarker microRNA(s) in subject blood sample. The invention also relates to kits comp
The present invention relates to panels of biomarker microRNAs for use in methods of diagnosing Alzheimer's disease and related diseases and conditions in a subject. The methods involve assessing the level of said biomarker microRNA(s) in subject blood sample. The invention also relates to kits comprising said panels of biomarker microRNAs, methods of diagnosing Alzheimer's disease and to the use of said panels of biomarker microRNAs in diagnosis.
대표청구항
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1. A panel of biomarker microRNAs for use in a method of diagnosing Alzheimer's disease and/or Mild Cognitive Impairment (MCI) due to Alzheimer's disease and/or Subjective Cognitive Impairment (SCI) due to Alzheimer's disease, in particular for the detection of an early stage of Alzheimer's disease
1. A panel of biomarker microRNAs for use in a method of diagnosing Alzheimer's disease and/or Mild Cognitive Impairment (MCI) due to Alzheimer's disease and/or Subjective Cognitive Impairment (SCI) due to Alzheimer's disease, in particular for the detection of an early stage of Alzheimer's disease in subjects with Mild Cognitive Impairment or with Subjective Cognitive Impairment and/or for diagnosis of Alzheimer's disease in patients with clinical dementia in a subject, characterized in that the panel comprises hsa-miR-483-5p (SEQ ID NO: 5) and hsa-miR-486-5p (SEQ ID NO: 3) and the method involves assessing the level of said biomarker microRNA(s) in subject blood sample. 2. The panel of biomarker microRNAs for use according to claim 1, characterized in that the panel comprises at least one additional biomarker microRNA(s) selected from the group consisting of hsa-miR-502-3p (SEQ ID NO: 14), hsa-miR-103a-3p (SEQ ID NO: 15), hsa-miR-301a-3p (SEQ ID NO: 16), hsa-miR-142-3p (SEQ ID NO: 17), hsa-miR-200a-3p (SEQ ID NO: 18), hsa-miR-1260a (SEQ ID NO: 19). 3. The panel of biomarker microRNAs for use according to claim 2, characterized in that the panel comprises hsa-miR-200a-3p (SEQ ID NO: 18). 4. The panel of biomarker microRNAs for use according to any of claims 1-3, characterized in that the panel comprises at least one, preferably two, preferably three, preferably four, preferably five, preferably six, preferably all seven biomarker microRNAs selected from hsa-miR-151a-5p (SEQ ID NO: 1), hsa-miR-30b-5p (SEQ ID NO: 2), hsa-miR-33a-5p (SEQ ID NO: 4), hsa-miR-18a-5p (SEQ ID NO: 6), hsa-miR-320a (SEQ ID NO: 7), hsa-miR-320b (SEQ ID NO: 8), hsa-miR-320c (SEQ ID NO: 9). 5. The panel of biomarker microRNAs for use according to any of claims 1-4, characterized in that the panel comprises hsa-miR-151a-5p (SEQ ID NO: 1), hsa-miR-30b-5p (SEQ ID NO: 2), hsa-miR-33a-5p (SEQ ID NO: 4), hsa-miR-18a-5p (SEQ ID NO: 6), hsa-miR-320a (SEQ ID NO: 7), hsa-miR-320b (SEQ ID NO: 8), and hsa-miR-320c (SEQ ID NO: 9). 6. The panel of biomarker microRNAs for use according to any of claims 1-5, characterized in that the panel comprises hsa-miR-502-3p (SEQ ID NO: 14), hsa-miR-103a-3p (SEQ ID NO: 15), hsa-miR-301a-3p (SEQ ID NO: 16), hsa-miR-142-3p (SEQ ID NO: 17), hsa-miR-200a-3p (SEQ ID NO: 18), and hsa-miR-1260a (SEQ ID NO: 19). 7. The panel of biomarker microRNAs for use according to any of claims 1-6, wherein the use includes diagnosing the progression of the disease. 8. The panel of biomarker microRNAs for use according to claim 7, wherein the level of hsa-miR-483-5p (SEQ ID NO: 5) is used in assessing the progression of the disease. 9. The panel of biomarker microRNAs for use according to any of claims 1-8, wherein the use includes differentiating whether the subject is suffering from Alzheimer's disease or Mild Cognitive Impairment due to Alzheimer's disease. 10. The panel of biomarker microRNAs for use according to claim 9, wherein the panel additionally includes at least one of microRNA(s) hsa-miR-423-5p (SEQ ID NO: 10) and/or hsamiR-126-5p (SEQ ID NO: 11) and/or hsa-miR-22-5p (SEQ ID NO: 12) and/or hsa-miR-335-3p (SEQ ID NO: 13). 11. The panel of biomarker microRNAs for use according to any of claims 1-10, wherein the blood sample used for assessment has a volume of at most about 0.6 ml. 12. The panel of biomarker microRNAs for use according to any of claims 1-11, wherein the assessment of the level of said biomarker microRNA(s) is done by a qRT-PCR method. 13. The panel of biomarker microRNAs for use according to any of claims 1-12, characterized in that the subject is human. 14. A kit for diagnosing Alzheimer's disease and/or Mild Cognitive Impairment (MCI) due to Alzheimer's disease and/or Subjective Cognitive Impairment (SCI) due to Alzheimer's disease, in particular for detection of an early stage of Alzheimer's disease in subjects with Mild Cognitive Impairment or with Subjective Cognitive Impairment and/or for diagnosis of Alzheimer's disease in patients with clinical dementia in a subject, wherein the kit comprises: instructions for use;means for separating plasma from blood cells to avoid hemolysis—means for RNA isolation and preferably RNA isolation controls;means for cDNA synthesis by reverse transcription, preferably with a cDNA synthesis control to evaluate the reaction; anda panel, preferably a qPCR panel, of primers for miRNA(s) to be used as biomarkers wherein the miRNA(s) to be used as biomarkers include hsa-miR-483-5p (SEQ ID NO: 5) and hsa-miR-486-5p (SEQ ID NO: 3), and optionally: preferably additionally at least one of hsa-miR-151a-5p (SEQ ID NO: 1), hsa-miR-30b-5p (SEQ ID NO: 2), hsa-miR-33a-5p (SEQ ID NO: 4), hsa-miR-18a-5p (SEQ ID NO: 6), hsa-miR-320a (SEQ ID NO: 7), hsa-miR-320b (SEQ ID NO: 8), hsa-miR-320c (SEQ ID NO: 9), preferably additionally at least one of hsa-miR-502-3p (SEQ ID NO: 14), hsa-miR-103a-3p (SEQ ID NO: 15), hsa-miR-301a-3p (SEQ ID NO: 16), hsa-miR-142-3p (SEQ ID NO: 17), hsamiR-200a-3p (SEQ ID NO: 18), hsa-miR-1260a (SEQ ID NO: 19), and/or preferably at least one of hsa-miR-423-5p (SEQ ID NO: 10) and/or hsa-miR-126-5p (SEQ ID NO: 11) and/or hsa-miR-22-5p (SEQ ID NO: 12) and/or hsa-miR-335-3p (SEQ ID NO: 13). 15. A method of diagnosing Alzheimer's disease and/or Mild Cognitive Impairment (MCI) due to Alzheimer's disease and/or Subjective Cognitive Impairment (SCI) due to Alzheimer's disease in particular for detection of an early stage of Alzheimer's disease in subjects with Mild Cognitive Impairment or with Subjective Cognitive Impairment and/or for diagnosis of Alzheimer's disease in patients with clinical dementia in a subject by analyzing a blood sample from said subject, characterized in that it involves the following steps:—in vitro assessment of a level of at least hsa-miR-483-5p (SEQ ID NO: 5) and hsa-miR-486-5p (SEQ ID NO: 3) as biomarker microRNAs in subject blood sample, and—comparison of the assessed level of biomarker microRNA(s) with the level observed for a nondemented control. 16. The method of claim 15, wherein additionally a level of at least one additional biomarker microRNA is assessed, wherein the additional biomarker microRNA is selected from the group consisting of hsa-miR-502-3p (SEQ ID NO: 14), hsa-miR-103a-3p (SEQ ID NO: 15), hsa-miR-301a-3p (SEQ ID NO: 16), hsa-miR-142-3p (SEQ ID NO: 17), hsa-miR-200a-3p (SEQ ID NO: 18), hsa-miR-1260a (SEQ ID NO: 19). 17. The method of claim 16, wherein the assessed biomarker microRNA(s) include hsa-miR-200a-3p (SEQ ID NO: 18). 18. The method of any one of claims 15-17, wherein the method involves assessing the level of at least one, preferably two, preferably three, preferably four, preferably five, preferably six, preferably all seven biomarker microRNAs selected form a group of hsa-miR-151a-5p (SEQ ID NO: 1), hsa-miR-30b-5p (SEQ ID NO: 2), hsa-miR-33a-5p (SEQ ID NO: 4), hsa-miR-18a-5p (SEQ ID PK/3700/AGR 37 NO: 6), hsa-miR-320a (SEQ ID NO: 7), hsa-miR-320b (SEQ ID NO: 8), hsa-miR-320c (SEQ ID NO: 9). 19. The method of claim 15, wherein the method involves assessing the level of (i) hsa-miR-151a-5p (SEQ ID NO: 1), hsa-miR-30b-5p (SEQ ID NO: 2), hsa-miR-33a-5p (SEQ ID NO: 4), hsa-miR-18a-5p (SEQ ID NO: 6), hsa-miR-320a (SEQ ID NO: 7), hsa-miR-320b (SEQ ID NO: 8), and hsa-miR-320c (SEQ ID NO: 9), and/or(ii) hsa-miR-502-3p (SEQ ID NO: 14), hsa-miR-103a-3p (SEQ ID NO: 15), hsa-miR-301a-3p (SEQ ID NO: 16), hsa-miR-142-3p (SEQ ID NO: 17), hsa-miR-200a-3p (SEQ ID NO: 18), and hsa-miR-1260a (SEQ ID NO: 19). 20. The method of any of claims 15-19, wherein the method includes diagnosing the progression of the disease. 21. The method of any of claims 15-20, wherein the method includes differentiating whether the subject is suffering from Alzheimer's disease or Mild Cognitive Impairment due to Alzheimer's disease. 22. The method of claim 21, wherein the method includes additional assessment of a level of at least one of biomarker microRNA(s) hsa-miR-423-5p (SEQ ID NO: 10) and/or hsa-miR-126-5p (SEQ ID NO: 11) and/or hsa-miR-22-5p (SEQ ID NO: 12) and/or hsa-miR-335-3p (SEQ ID NO: 13). 23. The method of any of claims 15-22, wherein the blood sample has a volume of at most about 0.6 ml. 24. The method of any of claims 15-23, wherein the assessment of the level of said biomarker microRNA(s) is done by a qRT-PCR method. 25. The method of any of claims 15-24, characterized in that the subject is human. 26. Use of a panel of biomarker microRNAs comprising hsa-miR-483-5p (SEQ ID NO: 5) and hsa-miR-486-5p (SEQ ID NO: 3) for diagnosing Alzheimer's disease and/or Mild Cognitive Impairment (MCI) due to Alzheimer's disease and/or Subjective Cognitive Impairment (SCI) due to Alzheimer's disease, in particular for detection of an early stage of Alzheimer's disease in subjects with Mild Cognitive Impairment or with Subjective Cognitive Impairment and/or for diagnosis of Alzheimer's disease in patients with clinical dementia in a subject by analyzing a blood sample of said subject. 27. The use of claim 26, wherein additionally a level of at least one additional biomarker microRNA is assessed, wherein the additional biomarker microRNA is selected from the group consisting of hsa-miR-502-3p (SEQ ID NO: 14), hsa-miR-103a-3p (SEQ ID NO: 15), hsa-miR-301a-3p (SEQ ID NO: 16), hsa-miR-142-3p (SEQ ID NO: 17), hsa-miR-200a-3p (SEQ ID NO: 18), hsa-miR-1260a (SEQ ID NO: 19). 28. The use of claim 26 or 27, wherein the assessed biomarker microRNA(s) include hsa-miR-200a-3p (SEQ ID NO: 18). 29. The use of any of claims 26-28, wherein the use involves assessing the level of at least one, preferably two, preferably three, preferably four, preferably five, preferably six, preferably all seven biomarker microRNAs selected form a group of hsa-miR-151a-5p (SEQ ID NO: 1), hsa-miR-30b-5p (SEQ ID NO: 2), hsa-miR-33a-5p (SEQ ID NO: 4), hsa-miR-18a-5p (SEQ ID NO: 6), hsa-miR-320a (SEQ ID NO: 7), hsa-miR-320b (SEQ ID NO: 8), hsa-miR-320c (SEQ ID NO: 9). 30. The use of claim 26, wherein the use involves assessing the level of (i) hsa-miR-151a-5p (SEQ ID NO: 1), hsa-miR-30b-5p (SEQ ID NO: 2), hsa-miR-33a-5p (SEQ ID NO: 4), hsa-miR-18a-5p (SEQ ID NO: 6), hsa-miR-320a (SEQ ID NO: 7), hsa-miR-320b (SEQ ID NO: 8), and hsa-miR-320c (SEQ ID NO: 9), and/or(ii) hsa-miR-502-3p (SEQ ID NO: 14), hsa-miR-103a-3p (SEQ ID NO: 15), hsa-miR-301a-3p (SEQ ID NO: 16), hsa-miR-142-3p (SEQ ID NO: 17), hsa-miR-200a-3p (SEQ ID NO: 18), and hsa-miR-1260a (SEQ ID NO: 19). 31. The use of any of claims 26-30, wherein the use includes diagnosing the progression of the disease. 32. The use of any of claims 26-31, wherein the use includes differentiating whether the subject is suffering from Alzheimer's disease or Mild Cognitive Impairment due to Alzheimer's disease. 33. The use of claim 32, wherein the use includes additional assessment of a level of at least one of biomarker microRNA(s) hsa-miR-423-5p (SEQ ID NO: 10) and/or hsa-miR-126-5p (SEQ ID NO: 11) and/or hsa-miR-22-5p (SEQ ID NO: 12) and/or hsa-miR-335-3p (SEQ ID NO: 13). 34. The use of any of claims 26-33, wherein the blood sample has a volume of at most about 0.6 ml. 35. The use of any of claims 26-34, wherein the assessment of the level of said biomarker microRNA(s) is done by a qRT-PCR method. 36. The use of any of claims 26-35, characterized in that the subject is human.
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