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Use of trpc6 mRNA levels in peripheral blood cells for early detection/diagnosis of senile dementia

a technology of peripheral blood cells and mrna, applied in the field of biotechnology, can solve the problems of low specificity and sensitivity of mmse, inability to detect ad by using ad-secretase inhibitors, and possible interference of many substrates with normal physiological functions of secretase inhibitors, so as to achieve the effect of reducing a levels

Inactive Publication Date: 2018-03-08
AGING WISE BIOTECH INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

This approach provides a reliable, early biomarker for AD diagnosis and a therapeutic agent with fewer side effects by specifically targeting β-amyloid production, enhancing diagnostic accuracy and treatment efficacy while minimizing adverse effects on other γ-secretase substrates.

Problems solved by technology

However, as a subjective test for diagnostic basis, the specificity and the sensitivity of MMSE are low.
However, clinical trials for treating AD by using γ-secretase inhibitor turned out to be unsuccessful.
Therefore, γ-secretase inhibitors may interfere the normal physiological functions of many substrates.
The clinical result showed that after taking Semagacestat, the cognitive function of the AD patients was declined, and the risk of skin cancer and the adverse gastrointestinal reaction were increased.

Method used

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  • Use of trpc6 mRNA levels in peripheral blood cells for early detection/diagnosis of senile dementia
  • Use of trpc6 mRNA levels in peripheral blood cells for early detection/diagnosis of senile dementia
  • Use of trpc6 mRNA levels in peripheral blood cells for early detection/diagnosis of senile dementia

Examples

Experimental program
Comparison scheme
Effect test

example 1 specific

Detection of TRPC6 mRNA Levels in the Peripheral Blood Cells of AD Patients

[0204]Blood samples (including patients and control) were collected from different hospitals and the groups were set as followed. Cell RNA was extracted and reverse-transcribed into cDNA. Real-time fluorescence quantitative PCR was performed for quantitative determination.

[0205]1.1 Comparison of TRPC6 mRNA Levels in the Peripheral Blood Cells Among the Following Groups:[0206]a. sporadic AD (n=40, mean age=80.55±5.25)[0207]b. age-matched non-AD control (n=45, mean age=78.69±5.63)[0208]c. young non-AD control (n=45, mean age=60.6±6.56)

[0209]The results show: TRPC6 mRNA levels in the peripheral blood cells of AD patients were significantly lower than those of age-matched non-AD control group (***P<0.001; n=40-45). There is no significant difference in the TRPC6 mRNA levels between age-matched and young non-AD controls (n=45). See FIG. 1A.

[0210]The results from larger sample size are quite similar to those in FIG...

example 2

tion of Relevance Between TRPC6 mRNA Level and Aβ in Cell and In Vivo

[0244]2.1 Cell Transfection Experiment

[0245]HEK293 (ATCC CRL-1573) cells were transfected with the Aβ precursor protein APP, and then the HEK293 cells were plated in 12-well plates according to the general methods till the density approached 80%. Each well was transfected with 1 ug plasmidusing Lipofectamine2000. After 48 hr, the protein expression was detected by immunoblotting, and the protein levels of TRPC6 and TRPC5 were detected under the overexpression of APP.

[0246]The results are shown as FIGS. 2A and 2B: the over-production of Aβ in cell models did not affect the mRNA or protein levels of TRPC6 and TRPC5 (mean±SE, n=3); wherein, the actin protein was internal control; ns referred to not significant.

[0247]2.2 Animal Experiments

[0248]Comparing APP / PS1 mice model to wild-type mice to decide whether the mRNA levels of TRPC6 and TRPC5 change after overproducing Aβ. Total RNA from peripheral blood cells and brai...

example 3

Determination of the Effect of Expressing TRPCs on Aβ in Cells and In Vivo

[0251]3.1 Determining the Effect of TRPCs Overexpression on Aβ Levels in HEK293APP Stable Cells

[0252]TRPC6 or TRPC5 was overexpressed in HEK293APP stable cell lines respectively (Cells were passaged into 12-well plates till the densities were close to 80%. Each well was transfected with 1 ug plasmid using Lipofectamine 2000, and the Aβ levels in the medium were determined with ELISA after 48 hr).

[0253]The results were shown in Table 1 and FIG. 3A.

TABLE 1OverexpressingHEK293APPEmptyOverexpressingOverexpressingStable cellVectorTRPC6TRPC5Aβ4010.6839 ± 0.073590.9900 ± 0.02548Aβ4210.6734 ± 0.069940.9488 ± 0.02053

[0254]3.2 to Investigate Whether Knocking Down TRPC6 or TRPC5 in Primary Cultured Rat Cortical Neurons could Increase Aβ Levels

[0255]Fetal rat was collected on the 17th day of SD rat pregnancy. Cortical neurons of the rat brains were separated, obtained, and electrotransfected by Nucleofector Device (Amaxa)...

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Abstract

The invention relates to the use of TRPC6 mRNA levels in peripheral blood cells for the early detection / diagnosis of senile dementia. Specifically, the present invention provides a classic transient receptor potential channel 6 (TRPC6) gene or protein thereof and the use of same in preparing a reagent or test kit for detecting or diagnosing Alzheimer's disease. The present invention further relates to a polypeptide used to prepare a medicament that treats AD, and relates to a composition of said polypeptide.

Description

RELATED APPLICATIONS[0001]This application is a divisional application of U.S. Ser. No. 14 / 765,715, filed on Aug. 4, 2015, which is a national stage filing under 35 U.S.C. § 371 of International Application PCT / CN2014 / 071325 entitled “USE OF TRPC6 MRNA LEVELS IN PERIPHERAL BLOOD CELLS FOR EARLY DETECTION / DIAGNOSIS OF SENILE DEMENTIA” filed Jan. 24, 2014, which claims priority to CN Application No. 201310044282.0, filed Feb. 4, 2013, the entire disclosure of each of which is incorporated by reference in its entirety.TECHNIQUE FIELD[0002]The present invention relates to the biotechnology field, specifically, relates to the use of Transient Receptor Potential Canonical 6 (TRPC6) gene or protein thereof, for preparing the reagent or kit for the prediction or diagnosis of Alzheimer disease (AD). The present invention also relates to a polypeptide and composition thereof for preparing a medicament for treating AD.BACKGROUND[0003]Alzheimer's disease, namely senile dementia, is the most com...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C12Q1/68A61K38/57C07K14/705A61K38/17A61K38/08
CPCA61K38/57C12Q2600/112C07K14/705C12Q2600/158A61K38/177A61K38/08C12Q1/6883A61K38/00C07K2319/03G01N33/6872G01N33/6896G01N2333/705G01N2800/2821A61P25/28A61P43/00
Inventor WANG, YIZHENGWANG, JUNFENGLU, RUI
Owner AGING WISE BIOTECH INC
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