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New Data Shows miR-9* as Potential Signature of Neurodegeneration in HD

DECEMBER 21, 2017
Mathew Shanley
New data published in the Orphanet Journal of Rare Diseases has concluded that the microRNA (miRNA) MiR-9* in peripheral leukocyte could potentially serve as a signature feature of neurodegeneration in Huntington’s disease (HD) patients.

Kuo-Hsuan Chang, M.D., of the Department of Neurology, Chang Gung Memorial Hospital Linkou Medical Center and College of Medicine, Chang Gung University, Taoyuan, Taiwan and colleagues examined the expression levels of MiR-9* and 12 other miRNA mutations in an attempt to employ these molecular alterations in peripheral tissues as biomarkers for the disease.

HD is an autosomal dominant neurodegenerative rare disease caused by an unstable CAG (cytosine-adenine-guanine) repeat expansion in the Huntingtin gene that leads to the production of a mutant form of the huntingtin protein. It is associated with a progressive neurodegeneration of striatum and cerebral cortex, and leads to neurotoxicity and is characterized by a combination of psychiatric manifestations and cognitive decline.

Previous studies have shown 10 of the 13 evaluated miRNAs to exhibit alterations in the brains of HD patients, and 3 are potential regulators of differentially-expressed genes. The study measured the expression levels of the following MiRNAs in peripheral leukocytes of a cohort including 36 HD patients, 8 PreHD carriers and 28 healthy controls (HCs): mirR-9, miR-9*, miR-10b, miR-29a, miR-29b, miR-132, miR-196a, miR-196b, miR-330, and miR-615.

Table 1 displays the demographic characteristics and blood biochemical parameters of those enrolled. Table 2 displays the miRNA levels in the peripheral leukocytes in patients enrolled.

Table 1.
  HD (n = 36) PreHD (n = 8) Healthy controls (n = 28)
Age (years) 45.58 ± 12.53 29.75 ± 7.21* 42.03 ± 11.01
Male (%) 20 (55.56) 3 (37.50) 17 (58.62)
HD duration (years) 4.38 ± 3.09    
Expanded CAG repeat number 46.42 ± 9.07 44.13 ± 3.17  
Drugs (%)
Dopamine antagonist 18 (50.00) 0 (0) 0 (0)
Anti-depressants (SSRI, SNRI, NaSSA) 9 (25.00) 0 (0) 0 (0)
Amantadine 5 (13.89) 0 (0) 0 (0)
UHDRS
Motor score 27.2 ± 18.94 0  
Independence scale 78.57 ± 21.98 100  
Functional capacity 9.31 ± 3.71 13  

Table 2.
miRNA HD (n = 36) PreHD (n = 8) Normal control (n = 28) P value
miR-9* 0.0008 ± 0.0013* 0.0008 ± 0.0011 0.0028 ± 0.0035 0.005
miR-9 0.0019 ± 0.0019 0.0007 ± 0.0008 0.0037 ± 0.0055 0.064
miR-1 0.0013 ± 0.0015 0.0018 ± 0.0022 0.0029 ± 0.0035 0.070
miR-330 0.0128 ± 0.0081 0.0208 ± 0.0157 0.0184 ± 0.0098 0.071
miR-29b 0.0023 ± 0.0043 0.0055 ± 0.0061 0.0038 ± 0.0039 0.075
miR-10b 0.0013 ± 0.0012 0.0024 ± 0.0029 0.0022 ± 0.0019 0.092
miR-615 0.0238 ± 0.0370 0.0080 ± 0.0074 0.0336 ± 0.0328 0.212
miR-196a 0.0072 ± 0.0063 0.0136 ± 0.0143 0.0122 ± 0.0139 0.252
miR-196b 0.0089 ± 0.0093 0.0146 ± 0.0156 0.0161 ± 0.0213 0.265
miR-155 0.0684 ± 0.0505 0.0928 ± 0.0765 0.0639 ± 0.0464 0.448
miR-132 0.0381 ± 0.0255 0.0476 ± 0.0346 0.0457 ± 0.0354 0.661
miR-29a 0.0926 ± 0.1003 0.1024 ± 0.0911 0.1136 ± 0.1368 0.841
miR-124a Not detectable Not detectable Not detectable  

In the study, it was made apparent that the MiR-9* plays a pivotal part in regulation of expression of neuron-specific genes, and could potentially serve as a potential therapeutic target for the disease.

While the results of the study clearly demonstrate the never-before-reported alterations of miRNA levels in peripheral leukocytes of HD patients, the study is limited by a small sample size, decreasing the power and influence of the statistics. A larger, multi-center, longitudinal study assessing the correlation of eripheral miRNA expression levels with clinical and neuroimaging features could potentially confirm the application of peripheral MiR-9* as biomarkers, and could clarify the association of MiR-9* with HD.

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