Methods of using miRNA from bodily fluids for early detection and monitoring of mild cognitive impairment (MCI) and Alzheimer's disease (AD)
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
C12Q-001/68
C12N-015/113
C12Q-001/6883
C12Q-001/6886
출원번호
US-0390110
(2016-12-23)
등록번호
US-10246747
(2019-04-02)
발명자
/ 주소
Umansky, Samuil R.
Sheinerman, Kira S.
Tsivinsky, Vladimir
출원인 / 주소
DiamiR, LLC
대리인 / 주소
Troutman Sanders LLP
인용정보
피인용 횟수 :
0인용 특허 :
19
초록
Described are methods for early diagnosis and progression monitoring of Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD) by quantifying neurite and/or synapse miRNAs in bodily fluids.
대표청구항▼
1. A method for identifying a compound useful for slowing down the progression of or treating pre-MCI or MCI, which method comprises: a. measuring the level of at least one synapse or neurite miRNA in one or more bodily fluid samples collected from a subject having pre-MCI or MCI, wherein the synaps
1. A method for identifying a compound useful for slowing down the progression of or treating pre-MCI or MCI, which method comprises: a. measuring the level of at least one synapse or neurite miRNA in one or more bodily fluid samples collected from a subject having pre-MCI or MCI, wherein the synapse or neurite miRNA is selected from the group consisting of miR-7, miR-125b, miR-128, miR-132, miR-874, miR-134, miR-323-3p, and miR-382, wherein said bodily fluid sample(s) is collected prior to test compound administration and wherein the bodily fluid is selected from the group consisting of blood plasma, serum, urine, and saliva;b. measuring the level of a normalizer miRNA in the same bodily fluid sample(s) as in step (a), wherein the normalizer miRNA is selected from the group consisting of miR-9, miR-181a, miR-127-3p, miR-370, miR-141, and miR-491-5p;c. calculating the ratio of the level of the synapse or neurite miRNA measured in step (a) to the level of the normalizer miRNA measured in step (b) for each of the bodily fluid samples collected from the subject prior to a test compound administration;d. measuring the level of the same synapse or neurite miRNA(s) as in step (a) in one or more bodily fluid samples collected from the subject following administration of the test compound, wherein the bodily fluid is selected from the group consisting of blood plasma, serum, urine, and saliva;e. measuring the level of the same normalizer miRNA as in step (b) in the same bodily fluid sample(s) as in step (d);f. calculating the ratio of the level of the synapse or neurite miRNA measured in step (d) to the level of the normalizer miRNA measured in step (e) for each of the bodily fluid samples collected from the subject following administration of the test compound;g. comparing the ratios of the levels of the miRNAs calculated in steps (c) and (f), andh. (i) identifying the test compound as a candidate compound for slowing down the progression of or treating pre-MCI or MCI if the ratio of the levels of the miRNAs calculated in step (f) is lower than the ratio of the levels of the miRNAs calculated in step (c); (ii) identifying the test compound as not a candidate compound for slowing down the progression of or treating pre-MCI or MCI if the ratio of the levels of the miRNAs calculated in step (f) is not lower than the ratio of the levels of the miRNAs calculated in step (c). 2. The method of claim 1, wherein the synapse or neurite miRNA is selected from the group consisting of miR-128, miR-132, miR-874, miR-134, miR-323-3p, and miR-382. 3. The method of claim 1, wherein the normalizer miRNA is selected from the group consisting of miR-9, miR-181a, miR-127-3p, miR-370, and miR-491-5p. 4. The method of claim 1, comprising measuring the level of two or more synapse or neurite miRNAs. 5. The method of claim 1, wherein said method comprises the step of administering the test compound to the subject. 6. The method of claim 1, which method comprises a step of collecting the bodily fluid sample from the subject prior to steps (a) and (d). 7. The method of claim 1, wherein the levels of the miRNAs are determined using RT-PCR. 8. The method of claim 1, wherein, prior to measuring miRNA levels, the miRNAs are purified from the bodily fluid sample. 9. The method of claim 1, which method comprises a step of reducing or eliminating degradation of the miRNAs. 10. A method for determining the effectiveness of a pre-MCI or MCI treatment in a subject, which method comprises: a. measuring the level of at least one synapse or neurite miRNA in one or more bodily fluid samples collected from the subject prior to initiation of the treatment, wherein the synapse or neurite miRNA is selected from the group consisting of miR-7, miR-125b, miR-128, miR-132, miR-874, miR-134, miR-323-3p, and miR-382 and wherein the bodily fluid is selected from the group consisting of blood plasma, serum, urine, and saliva;b. measuring the level of a normalizer miRNA in the same bodily fluid sample(s) as in step (a), wherein the normalizer miRNA is selected from the group consisting of miR-9, miR-181a, miR-127-3p, miR-370, miR-141, and miR-491-5p;c. calculating the ratio of the level of the synapse or neurite miRNA measured in step (a) to the level of the normalizer miRNA measured in step (b) for each of the bodily fluid samples collected from the subject prior to initiation of the treatment;d. measuring the level of the same synapse or neurite miRNA as in step (a) in one or more bodily fluid samples collected from the subject in the course of or following the treatment, wherein the bodily fluid is selected from the group consisting of blood plasma, serum, urine, and saliva;e. measuring the level of the same normalizer miRNA as in step (b) in the same bodily fluid sample(s) as in step (d);f. calculating the ratio of the level of the synapse or neurite miRNA measured in step (d) to the level of the normalizer miRNA measured in step (e) for each of the bodily fluid samples collected from the subject in the course of or following the treatment;g. comparing the ratios of the levels of the miRNAs calculated in steps (c) and (f), andh. (i) determining that the treatment is effective if the ratio of the levels of the miRNAs calculated in step (f) is lower than the ratio of the levels of the miRNAs calculated in step (c); (ii) determining that the treatment is not effective if the ratio of the levels of the miRNAs calculated in step (f) is not lower than the ratio of the levels of the miRNAs calculated in step (c). 11. The method of claim 10, wherein the subject does not have clinical symptoms of dementia. 12. The method of claim 10, wherein the synapse or neurite miRNA is selected from the group consisting of miR-128, miR-132, miR-874, miR-134, miR-323-3p, and miR-382. 13. The method of claim 10, wherein the normalizer miRNA is selected from the group consisting of miR-9, miR-181a, miR-127-3p, miR-370, and miR-491-5p. 14. The method of claim 10, comprising measuring the level of two or more synapse or neurite miRNAs. 15. The method of claim 10, wherein said method comprises the step of administering the treatment to the subject. 16. The method of claim 10, which method comprises a step of collecting the bodily fluid sample from the subject prior to steps (a) and (d). 17. The method of claim 10, wherein the levels of the miRNAs are determined using RT-PCR. 18. The method of claim 10, wherein, prior to measuring miRNA levels, the miRNAs are purified from the bodily fluid sample. 19. The method of claim 10, which method comprises a step of reducing or eliminating degradation of the miRNAs.
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