US2021040561A1PendingUtilityA1
Microglia Microvesicles Contained MicroRNA-Based Methods for the Diagnosis, Prognosis and Treatment Monitoring of Neurological, Neurodegenerative and Inflammation-Based Diseases
Est. expiryNov 20, 2035(~9.3 yrs left)· nominal 20-yr term from priority
C12Q 2600/178C12Q 1/6883C12N 2310/141C12N 15/113C12Q 2600/158C12Q 1/6886
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Claims
Abstract
The present invention describes a method for the in vitro diagnosis, prognosis and/or treatment monitoring of neurodegenerative, neurological and inflammation-based diseases, wherein the method comprises the steps: a) isolating microglial microvesicles (MVs) from biological fluids obtained from an individual; b) collecting the microRNA (miRNA) contained into said MVs; c) determining the expression profile of a predetermined set of miRNA; d) comparing said expression profile to one or several reference expression profiles, wherein the comparison of said determined expression profile to said one or several reference expression profiles allows for the diagnosis, prognosis and/or treatment monitoring of the disease.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A method for the in vitro diagnosis, prognosis and/or treatment monitoring of neurodegenerative, neurological or inflammation-based diseases, wherein the method comprises the steps:
a) isolating microglial microvesicles (MVs) from biological fluids obtained from an individual; b) collecting the miRNA contained into said MVs; c) determining the expression profile of a predetermined set of miRNA, defining a microglial MVs miRNA pattern; d) comparing said expression profile to one or several reference expression profiles, wherein the comparison of said determined expression profile to said one or several reference expression profiles allows for the diagnosis, prognosis and/or treatment monitoring of the disease.
2 . The method according to claim 1 , wherein said expression profile is determined of miRNAs selected from the group consisting of miR-125a-5p (SEQ ID 1), miR-300-3p (SEQ ID 2), miR-330-3p (SEQ ID 3), miR-466n-3p (SEQ ID 4), miR-501-5p (SEQ ID 5), miR-146a-5p (SEQ ID 6), miR-24-1-5p (SEQ ID 7), miR-1306-5p (SEQ ID 8), miR-744-5p (SEQ ID 9), miR-671-5p (SEQ ID 10), miR-134-5p (SEQ ID 11), miR-877-5p (SEQ ID 12), miR-23b-5p (SEQ ID 13), miR-669c-5p (SEQ ID 14), miR-29b-3p (SEQ ID 15), miR-195a-5p (SEQ ID 16), miR-151-5p (SEQ ID 17), miR-374c-3p (SEQ ID 18), miR-6539 (SEQ ID 19), miR-16-1-3p (SEQ ID 20), miR-6399 (SEQ ID 21), miR-6240 (SEQ ID 22), miR-23a-5p (SEQ ID 23), miR-92a-1-5p (SEQ ID 24), miR-219a-1-3p (SEQ ID 25), miR-128-1-5p (SEQ ID 26), miR-1949 (SEQ ID 27), miR-872-3p (SEQ ID 28), miR-582-3p (SEQ ID 29), miR-338-5p (SEQ ID 30), miR-379-5p (SEQ ID 31), miR-155-5p (SEQ ID 32), miR-450a-5p (SEQ ID 33), miR-100-5p (SEQ ID 34), miR-152-3p (SEQ ID 35), miR-222-3p (SEQ ID 36), let-7e (SEQ ID 37), miR-18b (SEQ ID 38), miR-19a (SEQ ID 39), miR-21b (SEQ ID 40), miR-26b (SEQ ID 41), miR-29b-1 (SEQ ID 42), miR-30c-1 (SEQ ID 43), miR-100 (SEQ ID 44), miR-130a (SEQ ID 45), miR-181c (SEQ ID 46), miR-297a-1 (SEQ ID 47), miR-330 (SEQ ID 48), miR-342 (SEQ ID 49), miR-484 (SEQ ID 50), miR-669b (SEQ ID 51), miR-669e (SEQ ID 52), miR-708 (SEQ ID 53), miR-146b (SEQ ID 54), miR-188 (SEQ ID 55), miR-346 (SEQ ID 56), miR-466f-3 (SEQ ID 57), miR-541 (SEQ ID 58), miR-706 (SEQ ID 59), miR-712 (SEQ ID 60), miR-714 (SEQ ID 61), miR-1224 (SEQ ID 62), miR-10b (SEQ ID 63), mir-22 (SEQ ID 64), mir-23b (SEQ ID 65), mir-132 (SEQ ID 66), mir-148b (SEQ ID 67), mir-154 (SEQ ID 68), mir-183 (SEQ ID 69), mir-337 (SEQ ID 70), mir-19b-1 (SEQ ID 71), mir-30a (SEQ ID 72), mir-33 (SEQ ID 73), mir-99b (SEQ ID 74), mir-144 (SEQ ID 75), mir-151 (SEQ ID 76), mir-182 (SEQ ID 77), mir-223 (SEQ ID 78), mir-340 (SEQ ID 79), mir-374b (SEQ ID 80), mir-432 (SEQ ID 81), mir-1247 (SEQ ID 82), let-7a-2 (SEQ ID 83), mir-30b (SEQ ID 84), mir-103-2 (SEQ ID 85), mir-107 (SEQ ID 86), mir-142a (SEQ ID 87), mir-146a (SEQ ID 88), mir-374c (SEQ ID 89), mir-126b (SEQ ID 90), mir-134 (SEQ ID 91), mir-320 (SEQ ID 92), let-7a-1 (SEQ ID 93), mir-34a (SEQ ID 94), mir-92b (SEQ ID 95), mir-211 (SEQ ID 96), let-7f-1 (SEQ ID 97), mir-19b-2 (SEQ ID 98), mir-137 (SEQ ID 99), mir-155 (SEQ ID 100), mir-219b (SEQ ID 101), mir-338 (SEQ ID 102), mir-376c (SEQ ID 103), mir-379 (SEQ ID 104), mir-451a (SEQ ID 105), mir-494 (SEQ ID 106), mir-17 (SEQ ID 107), mir-20a (SEQ ID 108), let-7c-1 (SEQ ID 109), mir-20b (SEQ ID 110), mir-145a (SEQ ID 111), mir-186 (SEQ ID 112), mir-664 (SEQ ID 113), mir-122 (SEQ ID 114), mir-409 (SEQ ID 115), miR-199b (SEQ ID 116), mir-221 (SEQ ID 117), mir-296 (SEQ ID 118), mir-329 (SEQ ID 119), mir-382 (SEQ ID 120), mir-29c (SEQ ID 121), mir-128-1 (SEQ ID 122), mir-138-1 (SEQ ID 123), mir-218-1 (SEQ ID 124), mir-222 (SEQ ID 125), mir-344-1 (SEQ ID 126), mir-466b-2 (SEQ ID 127), mir-674 (SEQ ID 128), mir-207 (SEQ ID 129), mir-18a (SEQ ID 130), mir-448 (SEQ ID 131), mir-669c (SEQ ID 133), let-7d (SEQ ID 134), mir-30e (SEQ ID 135), mir-34b (SEQ ID 136), mir-98 (SEQ ID 137), mir-124-1 (SEQ ID 138), mir-181a-1 (SEQ ID 139), mir-181b-1 (SEQ ID 140), mir-181d (SEQ ID 141), mir-185 (SEQ ID 142), mir-187 (SEQ ID 143), mir-190a (SEQ ID 144), mir-191 (SEQ ID 145), mir-301a (SEQ ID 146), mir-325 (SEQ ID 147), mir-331 (SEQ ID 148), mir-345 (SEQ ID 149), mir-361 (SEQ ID 150), mir-380 (SEQ ID 151), mir-381 (SEQ ID 152), mir-450a-2 (SEQ ID 153), mir-497a (SEQ ID 246), mir-497b (SEQ ID 155), mir-505 (SEQ ID 156), mir-551b (SEQ ID 157), mir-742 (SEQ ID 158), mir-875 (SEQ ID 159), mir-935 (SEQ ID 160), mir-21a (SEQ ID 161), mir-24-2 (SEQ ID 162), mir-27b (SEQ ID 163), mir-31 (SEQ ID 164), mir-34c (SEQ ID 165), mir-129-1 (SEQ ID 166), mir-140 (SEQ ID 167), mir-142b (SEQ ID 168), mir-148a (SEQ ID 169), mir-152 (SEQ ID 170), mir-184 (SEQ ID 171), mir-199a-1 (SEQ ID 172), mir-204 (SEQ ID 173), mir-212 (SEQ ID 174), mir-214 (SEQ ID 175), mir-375 (SEQ ID 176), mir-455 (SEQ ID 177), mir-711 (SEQ ID 178), mir-882 (SEQ ID 179), mir-192 (SEQ ID 180), mir-219a-1 (SEQ ID 181), mir-383 (SEQ ID 182), mir-542 (SEQ ID 183), mir-700 (SEQ ID 184), mir-705 (SEQ ID 185), mir-762 (SEQ ID 186), mir-1901 (SEQ ID 187), mir-1928 (SEQ ID 188), mir-3474 (SEQ ID 189), mir-105 (SEQ ID 190), mir-141 (SEQ ID 191), mir-200c (SEQ ID 192), mir-201 (SEQ ID 193), mir-297b (SEQ ID 194), mir-302c (SEQ ID 195), mir-495 (SEQ ID 196), mir-670 (SEQ ID 197), mir-673 (SEQ ID 198), mir-1934 (SEQ ID 199), mir-129b (SEQ ID 200), mir-328 (SEQ ID 201), mir-487b (SEQ ID 202), let-7b (SEQ ID 203), mir-292b (SEQ ID 204), mir-125b-2 (SEQ ID 205), mir-365-1 (SEQ ID 206), mir-32 (SEQ ID 207), mir-125a (SEQ ID 208), mir-128-2 (SEQ ID 209), mir-135a-1 (SEQ ID 210), mir-139 (SEQ ID 211), mir-149 (SEQ ID 212), mir-181a-2 (SEQ ID 213), mir-326 (SEQ ID 214), mir-483 (SEQ ID 215), mir-491 (SEQ ID 216), let-7c (SEQ ID 217), mir-9-1 (SEQ ID 218), mir-15b (SEQ ID 219), mir-16-1 (SEQ ID 220), mir-21 (SEQ ID 221), mir-23a (SEQ ID 222), mir-24-1 (SEQ ID 223), mir-25 (SEQ ID 224), mir-27a (SEQ ID 225), mir-92a-1 (SEQ ID 226), mir-93 (SEQ ID 227), mir-103a-1 (SEQ ID 228), mir-106b (SEQ ID 229), mir-125b-1 (SEQ ID 230), mir-150 (SEQ ID 231), mir-210 (SEQ ID 232), mir-718 (SEQ ID 233), mir-335 (SEQ ID 234), mir-297 (SEQ ID 235), mir-466 (SEQ ID 236), mir-151a (SEQ ID 237), mir-126 (SEQ ID 238), mir-320a (SEQ ID 239), mir-329-5p (SEQ ID 240), mir-497-5p (SEQ ID 241), mir-664a-5p (SEQ ID 242), mir-21-5p (SEQ ID 243), mir-142-5p (SEQ ID 244), mir-129-5p (SEQ ID 245), mir-146b (SEQ ID 154).
3 . The method according to claim 1 , wherein said diseases are neurodegenerative disease.
4 . The method according to claim 1 , wherein said disease is Parkinson's Disease (PD) and said microglial MVs miRNA pattern, with respect to said reference pattern, is characterised as follows:
downregulated miRNA: miR-100-5p (SEQ ID 34), miR-152-3p (SEQ ID 35), miR-155-5p (SEQ ID 32), miR-1949 (SEQ ID 27), miR-501-5p (SEQ ID 5), miR-6399 (SEQ ID 21), miR-872-3p (SEQ ID 28); upregulated miRNA: miR-128-1-5p (SEQ ID 26), miR-16-1-3p (SEQ ID 20), miR-219a-1-3p (SEQ ID 25), miR-222-3p (SEQ ID 36), miR-23a-5p (SEQ ID 23), miR-338-5p (SEQ ID 30), miR-379-5p (SEQ ID 31), miR-450a-5p (SEQ ID 33), miR-582-3p (SEQ ID 29), miR-6240 (SEQ ID 22), miR-92a-1-5p (SEQ ID 24).
5 . The method according to claim 1 , wherein said disease is PD and said microglial MVs miRNA pattern, with respect to said reference pattern, is characterised as follows:
downregulated miRNA: miR-100-5p (SEQ ID 34), miR-152-3p (SEQ ID 35), miR-1949 (SEQ ID 27), miR-501-5p (SEQ ID 5); upregulated miRNA: miR-128-1-5p (SEQ ID 26), miR-16-1-3p (SEQ ID 20), miR-219a-1-3p (SEQ ID 25), miR-222-3p (SEQ ID 36), miR-23a-5p (SEQ ID 23), miR-338-5p (SEQ ID 30), miR-379-5p (SEQ ID 31), miR-450a-5p (SEQ ID 33), miR-582-3p (SEQ ID 29), miR-92a-1-5p (SEQ ID 24).
6 . The method according to claim 1 , wherein said disease is Alzheimer's Disease (AD) and said microglial MVs miRNA pattern, with respect to said reference pattern, is characterised as follows:
downregulated miRNA: miR-151-5p (SEQ ID 17), miR-23b-5p (SEQ ID 13), miR-374c-3p (SEQ ID 18), miR-669c-5p (SEQ ID 14); upregulated miRNA: miR-501-5p (SEQ ID 5), miR-125a-5p (SEQ ID 1), miR-1306-5p (SEQ ID 8), miR-134-5p (SEQ ID 11), miR-146a-5p (SEQ ID 6), miR-24-1-5p (SEQ ID 7), miR-300-3p (SEQ ID 2), miR-330-3p (SEQ ID 3), miR-466n-3p (SEQ ID 4), miR-671-5p (SEQ ID 10), miR-744-5p (SEQ ID 9), miR-877-5p (SEQ ID 12).
7 . The method according to claim 1 , wherein said disease is Alzheimer's Disease and said microglial MVs miRNA pattern, with respect to said reference pattern, is characterised as follows:
downregulated miRNA: miR-151-5p (SEQ ID 17), miR-23b-5p (SEQ ID 13), miR-374c-3p (SEQ ID 18); upregulated miRNA: miR-501-5p (SEQ ID 5), miR-125a-5p (SEQ ID 1), miR-1306-5p (SEQ ID 8), miR-134-5p (SEQ ID 11), miR-146a-5p (SEQ ID 6), miR-24-1-5p (SEQ ID 7), miR-300-3p (SEQ ID 2), miR-330-3p (SEQ ID 3), miR-671-5p (SEQ ID 10), miR-744-5p (SEQ ID 9), miR-877-5p (SEQ ID 12).
8 . The method according to claim 1 , wherein said disease is ischemia and a pattern of at least 16, preferably at least 20 of the miRNA listed in Table 3 is an indicator of ischemia (+, upregulated; −, downregulated with respect to said reference pattern);
TABLE 3
miRNA
let-7e (SEQ ID 37)
−
mir-18b (SEQ ID 38)
−
mir-19a (SEQ ID 39)
−
mir-21 (SEQ ID 221)
−
mir-26b (SEQ ID 41)
−
mir-29b-1 (SEQ ID 42)
−
mir-30c-1 (SEQ ID 43)
−
mir-100 (SEQ ID 44)
−
mir-130a (SEQ ID 45)
−
mir-181c (SEQ ID 46)
−
mir-297 (SEQ ID 235)
−
mir-330 (SEQ ID 48)
−
mir-342 (SEQ ID 49)
−
mir-484 (SEQ ID 50)
−
mir-669b (SEQ ID 51)
−
mir-669e (SEQ ID 52)
−
mir-708 (SEQ ID 53)
−
mir-146b (SEQ ID 54)
+
mir-188 (SEQ ID 55)
+
mir-346 (SEQ ID 56)
+
mir-466 (SEQ ID 236)
+
mir-541 (SEQ ID 58)
+
mir-706 (SEQ ID 59)
+
mir-712 (SEQ ID 60)
+
mir-714 (SEQ ID 61)
+
mir-1224 (SEQ ID 62)
+
9 . The method according to claim 1 , wherein said disease is Tourette's Syndrome and a pattern of at least 13, preferably at least 16 of the miRNA listed in Table 4 is an indicator of Tourette's Syndrome (+, upregulated; −, downregulated with respect to said reference pattern);
TABLE 4
miRNA
mir-10b (SEQ ID 63)
−
mir-22 (SEQ ID 64)
−
mir-23b (SEQ ID 65)
−
mir-132 (SEQ ID 66)
−
mir-148b (SEQ ID 67)
−
mir-154 (SEQ ID 68)
−
mir-183 (SEQ ID 69)
−
mir-337 (SEQ ID 70)
−
mir-1224 (SEQ ID 62)
−
mir-19b-1 (SEQ ID 71)
+
mir-30a (SEQ ID 72)
+
mir-33 (SEQ ID 73)
+
mir-99b (SEQ ID 74)
+
mir-144 (SEQ ID 75)
+
mir-151a (SEQ ID 237)
+
mir-182 (SEQ ID 77)
+
mir-223 (SEQ ID 78)
+
mir-340 (SEQ ID 79)
+
mir-374b (SEQ ID 80)
+
mir-1247 (SEQ ID 82)
+
mir-432 (SEQ ID 81)
+
10 . The method according to claim 1 , wherein said disease is neuropathic pain and a pattern of at least 8, preferably at least 10 of the miRNA listed in Table 5 is an indicator of neuropathic pain (+, upregulated; −, downregulated with respect to said reference pattern);
TABLE 5
miRNA
let-7a-2 (SEQ ID 83)
−
mir-30b (SEQ ID 84)
−
mir-103-2 (SEQ ID 85)
−
mir-107 (SEQ ID 86)
−
mir-142a (SEQ ID 87)
−
mir-146a (SEQ ID 88)
−
mir-151 (SEQ ID 76)
−
mir-374c (SEQ ID 89)
−
mir-126 (SEQ ID 238)
+
mir-134 (SEQ ID 91)
+
mir-320a (SEQ ID 239)
+
mir-374b (SEQ ID 80)
+
11 . The method according to claim 1 , wherein said disease is autism and a pattern of at least 13, preferably at least 16 of the miRNA listed in Table 6 is an indicator of autism (+, upregulated; −, downregulated with respect to said reference pattern);
TABLE 6
miRNA
let-7a-1 (SEQ ID 93)
−
mir-34a (SEQ ID 94)
−
mir-92b (SEQ ID 95)
−
mir-211 (SEQ ID 96)
−
let-7f-1 (SEQ ID 97)
+
mir-19a (SEQ ID 39)
+
mir-19b-2 (SEQ ID 98)
+
mir-21 (SEQ ID 221)
+
mir-22 (SEQ ID 64)
+
mir-137 (SEQ ID 99)
+
mir-142a (SEQ ID 87)
+
mir-144 (SEQ ID 75)
+
mir-146b (SEQ ID 154)
+
mir-155 (SEQ ID 100)
+
mir-219b (SEQ ID 101)
+
mir-338 (SEQ ID 102)
+
mir-376c (SEQ ID 103)
+
mir-379 (SEQ ID 104)
+
mir-451a (SEQ ID 105)
+
mir-494 (SEQ ID 106)
+
12 . The method according to claim 1 , wherein said disease is multiple sclerosis and a pattern of at least 7 of the miRNA listed in Table 7 is an indicator of multiple sclerosis (+, upregulated; −, downregulated with respect to said reference pattern);
TABLE 7
miRNA
mir-17 (SEQ ID 107)
−
mir-20a (SEQ ID 108)
−
let-7c-1 (SEQ ID 109)
+
mir-20b (SEQ ID 110)
+
mir-142a (SEQ ID 87)
+
mir-145a (SEQ ID 111)
+
mir-186(SEQ ID 112)
+
mir-223 (SEQ ID 78)
+
mir-664 (SEQ ID 113)
+
13 . The method according to claim 1 , wherein said disease is Rett Syndrome and a pattern of at least 10 of the miRNA listed in Table 8 is an indicator of Rett Syndrome (+, upregulated; −, downregulated with respect to said reference pattern);
TABLE 8
miRNA
mir-122 (SEQ ID 114)
−
mir-130a (SEQ ID 45)
−
mir-146a (SEQ ID 88)
−
mir-146b (SEQ ID 54)
−
mir-342 (SEQ ID 49)
−
mir-409 (SEQ ID 115)
−
mir-29b-1 (SEQ ID 42)
+
mir-92b (SEQ ID 95)
+
mir-199b (SEQ ID 116)
+
mir-221 (SEQ ID 117)
+
mir-296 (SEQ ID 118)
+
mir-329-5p (SEQ ID 240)
+
mir-382 (SEQ ID 120)
+
14 . The method according to claim 1 , wherein said disease is Huntington's Disease and a pattern of at least 12 of the miRNA listed in Table 9 is an indicator of autism (+, upregulated; −, downregulated with respect to said reference pattern);
TABLE 9
miRNA
mir-22 (SEQ ID 64)
−
mir-29c (SEQ ID 121)
−
mir-128-1 (SEQ ID 122)
−
mir-132 (SEQ ID 66)
−
mir-138-1 (SEQ ID 123)
−
mir-218-1 (SEQ ID 124)
−
mir-222 (SEQ ID 125)
−
mir-344-1 (SEQ ID 126)
−
mir-466 (SEQ ID 236)
−
mir-674 (SEQ ID 128)
−
mir-34a (SEQ ID 94)
+
mir-207 (SEQ ID 129)
+
mir-18a (SEQ ID 130)
+
mir-448 (SEQ ID 131)
+
mir-669c (SEQ ID 133)
+
15 . The method according to claim 1 , wherein said disease is epilepsy and a pattern of at least 31, preferably at least 42 of the miRNA listed in Table 10 is an indicator of epilepsy (+, upregulated; −, downregulated with respect to said reference pattern);
TABLE 10
miRNA
let-7d (SEQ ID 134)
−
let-7f-1 (SEQ ID 97)
−
mir-30a (SEQ ID 72)
−
mir-30e (SEQ ID 135)
−
mir-34b (SEQ ID 136)
−
mir-98 (SEQ ID 137)
−
mir-124-1 (SEQ ID 138)
−
mir-181a-1 (SEQ ID 139)
−
mir-181b-1 (SEQ ID 140)
−
mir-181d (SEQ ID 141)
−
mir-185 (SEQ ID 142)
−
mir-186 (SEQ ID 112)
−
mir-187 (SEQ ID 143)
−
mir-190a (SEQ ID 144)
−
mir-191 (SEQ ID 145)
−
mir-301a (SEQ ID 146)
−
mir-325 (SEQ ID 147)
−
mir-331 (SEQ ID 148)
−
mir-345 (SEQ ID 149)
−
mir-361 (SEQ ID 150)
−
mir-374b (SEQ ID 80)
−
mir-380 (SEQ ID 151)
−
mir-381 (SEQ ID 152)
−
mir-450a-2 (SEQ ID 153)
−
mir-497a (SEQ ID 246)
−
mir-497-5p (SEQ ID 241)
−
mir-505 (SEQ ID 156)
−
mir-551b (SEQ ID 157)
−
mir-664a-5p (SEQ ID 242)
−
mir-742 (SEQ ID 158)
−
mir-875 (SEQ ID 159)
−
mir-935 (SEQ ID 160)
−
mir-17 (SEQ ID 107)
+
mir-21-5p (SEQ ID 243)
+
mir-23b (SEQ ID 65)
+
mir-24-2 (SEQ ID 162)
+
mir-27b (SEQ ID 163)
+
mir-31 (SEQ ID 164)
+
mir-34c (SEQ ID 165)
+
mir-129-1 (SEQ ID 166)
+
mir-140 (SEQ ID 167)
+
mir-142-5p (SEQ ID 244)
+
mir-148a (SEQ ID 169)
+
mir-152 (SEQ ID 170)
+
mir-184 (SEQ ID 171)
+
mir-199a-1 (SEQ ID 172)
+
mir-204 (SEQ ID 173)
+
mir-212 (SEQ ID 174)
+
mir-214 (SEQ ID 175)
+
mir-375 (SEQ ID 176)
+
mir-455 (SEQ ID 177)
+
mir-711 (SEQ ID 178)
+
mir-882 (SEQ ID 179)
+
16 . The method according to claim 1 , wherein said disease is glioblastoma and a pattern of at least 33, preferably at least 44 of the miRNA listed in Table 11 is an indicator of glioblastoma (+, upregulated; −, downregulated with respect to said reference pattern);
TABLE 11
miRNA
mir-29b-1 (SEQ ID 42)
−
mir-32 (SEQ ID 207)
−
mir-34a (SEQ ID 94)
−
mir-100 (SEQ ID 44)
−
mir-124-1 (SEQ ID 138)
−
mir-125a (SEQ ID 208)
−
mir-128-1 (SEQ ID 122)
−
mir-128-2 (SEQ ID 209)
−
mir-129-1 (SEQ ID 166)
−
mir-132 (SEQ ID 66)
−
mir-135a-1 (SEQ ID 210)
−
mir-137 (SEQ ID 99)
−
mir-138-1 (SEQ ID 123)
−
mir-139 (SEQ ID 211)
−
mir-146b (SEQ ID 54)
−
mir-149 (SEQ ID 212)
−
mir-181a-2 (SEQ ID 213)
−
mir-181b-1 (SEQ ID 140)
−
mir-181d (SEQ ID141)
−
mir-184 (SEQ ID 171)
−
mir-185 (SEQ ID 142)
−
mir-218-1 (SEQ ID 124)
−
mir-326 (SEQ ID 214)
−
mir-483 (SEQ ID 215)
−
mir-491 (SEQ ID 216)
−
let-7c (SEQ ID 217)
+
mir-9-1 (SEQ ID 218)
+
mir-15b (SEQ ID 219)
+
mir-16-1 (SEQ ID 220)
+
mir-17 (SEQ ID 107)
+
mir-19b-1 (SEQ ID 71)
+
mir-20a (SEQ ID 108)
+
mir-21 (SEQ ID 221)
+
mir-23a (SEQ ID 222)
+
mir-24-1 (SEQ ID 223)
+
mir-25 (SEQ ID 224)
+
mir-27a (SEQ ID 225)
+
mir-30b (SEQ ID 84)
+
mir-92a-1 (SEQ ID 226)
+
mir-93 (SEQ ID 227)
+
mir-103a-1 (SEQ ID 228)
+
mir-106b (SEQ ID 229)
+
mir-125b-1 (SEQ ID 230)
+
mir-146a (SEQ ID 88)
+
mir-150 (SEQ ID 231)
+
mir-155 (SEQ ID 100)
+
mir-182 (SEQ ID 77)
+
mir-183 (SEQ ID 69)
+
mir-210 (SEQ ID 232)
+
mir-221 (SEQ ID 117)
+
mir-223 (SEQ ID 78)
+
mir-328 (SEQ ID 201)
+
mir-381 (SEQ ID 152)
+
mir-451a (SEQ ID 105)
+
mir-718 (SEQ ID 233)
+
mir-335 (SEQ ID 234)
+
17 . The method according to claim 1 , wherein said disease is meningitis and a pattern of at least 16, preferably at least 21 of the miRNA listed in Table 12 is an indicator of meningitis (+, upregulated; −, downregulated with respect to said reference pattern);
TABLE 12
miRNA
mir-138-1 (SEQ ID 123)
−
mir-192 (SEQ ID 180)
−
mir-219a-1 (SEQ ID 181)
−
mir-383 (SEQ ID 182)
−
mir-466 (SEQ ID 236)
−
mir-542 (SEQ ID 183)
−
mir-700 (SEQ ID 184)
−
mir-705 (SEQ ID 185)
−
mir-762 (SEQ ID 186)
−
mir-1901 (SEQ ID 187)
−
mir-1928 (SEQ ID 188)
−
mir-3474 (SEQ ID 189)
−
let-7a-1 (SEQ ID 93)
+
mir-10b (SEQ ID 63)
+
mir-105 (SEQ ID 190)
+
mir-141 (SEQ ID 191)
+
mir-155 (SEQ ID 100)
+
mir-191 (SEQ ID 145)
+
mir-200c (SEQ ID 192)
+
mir-201 (SEQ ID 193)
+
mir-214 (SEQ ID 175)
+
mir-297b (SEQ ID 194)
+
mir-302c (SEQ ID 195)
+
mir-495 (SEQ ID 196)
+
mir-670 (SEQ ID 197)
+
mir-673 (SEQ ID 198)
+
mir-1934 (SEQ ID 199)
+
18 . The method according to claim 1 , wherein said disease is traumatic brain injury and a pattern of at least 12 of the miRNA listed in Table 13 is an indicator of traumatic brain injury (+, upregulated; −, downregulated with respect to said reference pattern);
TABLE 13
miRNA
mir-129-5p (SEQ ID 245)
−
mir-140 (SEQ ID 167)
−
mir-185 (SEQ ID 142)
−
mir-212 (SEQ ID 174)
−
mir-328 (SEQ ID 201)
−
mir-361 (SEQ ID 150)
−
mir-487b (SEQ ID 202)
−
let-7a-2 (SEQ ID 83)
+
let-7b (SEQ ID 203)
+
mir-19b-1 (SEQ ID 71)
+
mir-21-5p (SEQ ID 243)
+
mir-126 (SEQ ID 238)
+
mir-146a (SEQ ID 88)
+
mir-155 (SEQ ID 100)
+
mir-223 (SEQ ID 78)
+
mir-292b (SEQ ID 204)
+
19 . The method according to claim 1 , wherein said disease is amyotrophic lateral sclerosis (ALS) and a pattern of at least 4 of the miRNA listed in Table 14 is an indicator of ALS (+, upregulated; −, downregulated with respect to said reference pattern);
TABLE 14
miRNA
mir-22 (SEQ ID 64)
+
mir-125b-2 (SEQ ID 205)
+
mir-146b (SEQ ID 54)
+
mir-155 (SEQ ID 100)
+
mir-214 (SEQ ID 175)
+
mir-365-1 (SEQ ID 206)
+
20 . The method according to claim 1 , wherein said disease is depression and a pattern of at least 5 of the miRNA listed in Table 15 is an indicator of depression (+, upregulated; −, downregulated with respect to said reference pattern);
TABLE 15
miRNA
mir-34a (SEQ ID 94)
−
mir-451a (SEQ ID 105)
−
mir-132 (SEQ ID 66)
+
mir-134 (SEQ ID 91)
+
mir-144 (SEQ ID 75)
+
mir-182 (SEQ ID 77)
+
mir-221 (SEQ ID 117)
+
21 . A kit for the diagnosis and prognosis of neurodegenerative, neurological and inflammation-based diseases, comprising:
a) means for determining the miRNA expression profile of a miRNA sample of microglial microvesicles of an individual, and b) at least one reference set of miRNA profile characteristic for said neurodegenerative, neurological and inflammation-based diseases.Join the waitlist — get patent alerts
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