Uses for prevention or treatment of brain diseases using microrna
Inventors
Ryu, Jin-Hyeob • Cho, Hyun-Jeong
Assignees
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Publication Number
US-10844380-B1
Publication Date
2020-11-24
Expiration Date
Abstract
The present disclosure relates to a pharmaceutical composition for preventing or treating a brain disease, more particularly to a pharmaceutical composition for preventing or treating a brain disease, which contains a miR-485-3p inhibitor, and a method for screening an agent for preventing or treating a brain disease, which includes a step of measuring the expression level of miR-485-3p. Because the composition for treating a brain disease, which contains a miR-485-3p inhibitor, can restore the ELAVL2 protein unlike the exiting therapeutic agents for Alzheimer's disease, which are limited only to alleviating symptoms by inducing decreased expression of amyloid beta 42, the present disclosure can fundamentally treat various diseases caused by decreased expression of ELAVL2, such as Alzheimer's disease, autism spectrum disorder, mental retardation, amyotrophic lateral sclerosis, etc. Therefore, the present disclosure is useful for treating brain diseases including Alzheimer's disease fundamentally.
Core Innovation
The disclosure provides a pharmaceutical approach for prevention and/or treatment of brain diseases by administering a miR-485-3p inhibitor. The miR-485-3p inhibitor is a nucleic acid molecule that inhibits expression of miR-485-3p. In the context of Alzheimer’s disease, miR-485-3p upregulation in Alzheimer’s patients and in a 5×FAD mouse model is linked to reduced ELAVL2 expression and increased amyloid beta 42 (Aβ42).
Inhibition of miR-485-3p with an miR-485-3p inhibitor, including an antagomir AM-485-3p; SEQ ID NO:9, 2′-O-methylated, restores ELAVL2 and reduces Aβ42 production. The disclosure also reports that miR-485-3p inhibition decreases APP and tau/p-tau and improves cognitive behavior in vivo. The approach can extend to other ELAVL2-associated neurological diseases beyond Alzheimer’s disease.
Claims Coverage
The partial content includes three independent claims focused on treating Alzheimer’s disease using a miR-485-3p inhibitor with specific nucleic-acid and antisense-oligonucleotide features. Across the independent claims, the inventive features are the use of a miR-485-3p expression inhibitor for treatment, and more specifically the inhibitor’s antisense binding sequences and defined antisense nucleotide sequence/chemistry.
Treating Alzheimer’s disease by administering a miR-485-3p inhibitor nucleic acid that inhibits miR-485-3p expression
A method of treating Alzheimer's disease in a subject in need thereof comprising administering a miR-485-3p inhibitor to the subject, wherein the miR-485-3p inhibitor is a nucleic acid molecule and inhibits expression of miR-485-3p.
Antisense oligonucleotide inhibitor binding to SEQ ID NO: 1 or SEQ ID NO: 2
A method of treating Alzheimer's disease in a subject in need thereof comprising administering a miR-485-3p inhibitor to the subject, wherein the miR-485-3p inhibitor comprises an antisense oligonucleotide that binds to the sequence as set forth in SEQ ID NO: 1 or SEQ ID NO: 2.
Antisense oligonucleotide comprising nucleotide sequence as set forth in SEQ ID NO: 7
A method of treating Alzheimer's disease in a subject in need thereof comprising administering a miR-485-3p inhibitor to the subject, wherein the miR-485-3p inhibitor comprises an antisense oligonucleotide that comprises the nucleotide sequence as set forth in SEQ ID NO: 7.
Overall, the claim set covers Alzheimer’s disease treatment by administering a miR-485-3p inhibitor that inhibits miR-485-3p expression, with additional independent-claim scope directed to antisense oligonucleotide binding to specified sequences (SEQ ID NO: 1 or SEQ ID NO: 2) and to an antisense oligonucleotide containing a defined nucleotide sequence (SEQ ID NO: 7).
Stated Advantages
Restores ELAVL2 expression.
Reduces Aβ42 production.
Decreases APP.
Decreases tau/p-tau.
Improves cognitive behavior in vivo.
Documented Applications
Prevention and/or treatment of brain diseases by administering a miR-485-3p inhibitor, including Alzheimer’s disease, with the disclosure connecting miR-485-3p upregulation to ELAVL2 and Aβ42 changes.
A screening method for candidate agents tested for decreasing miR-485-3p expression.
Extension of applicability to other ELAVL2-associated neurological diseases beyond Alzheimer’s disease.
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