# US 10,119,140 B2 · Methods for enhancing or decreasing the levels of MIR124 and MIR29 in subjects with muscular dystrophy

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- Number: US 10,119,140 B2
- Document ID: US10119140B2
- Status: Granted
- Kind: B2
- Application number: 15/305,058
- Filed: 2015-04-17
- Published: 2017-03-30
- Granted: 2018-11-06
- Earliest claimed: 2014-04-18
- Assignees: Board of Regents of the Nevada System of Higher Education, on behalf of the University of Nevada, Reno
- Applicants: Board of Regents of the Nevada System of Higher Education, on Behalf of The University of Nevada
- Inventors: Cherie A. Singer; Ryan Wuebbles; Dean Burkin
- Web page: https://patentgrep.com/patent/US10119140B2

## CPC

- C12N 15/113: Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)}
- A61K 31/713: Double-stranded nucleic acids or oligonucleotides
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- A61P 21/04: for myasthenia gravis
- C12N 15/111: {General methods applicable to biologically active non-coding nucleic acids}
- C12Q 1/6883: for diseases caused by alterations of genetic material
- C12N 2310/113: targeting other non-coding nucleic acids, e.g. antagomirs
- C12N 2310/141: MicroRNAs, miRNAs
- C12N 2320/30: Special therapeutic applications
- C12Q 2600/158: Expression markers
- C12Q 2600/178: miRNA, siRNA or ncRNA
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES

## Abstract

Disclosed herein are methods of treating and diagnosing muscular dystrophy. In some examples, the methods include treating muscular dystrophy by administering to the subject a therapeutically effective amount of an agent that alters the expression of at least one miR gene product, such as miRNA-124 and/or miRNA-29 thereby treating muscular dystrophy. In one particular example, the method of treatment includes administering an agent that decreases the expression or activity of miRNA-124. In another embodiment, the method of treatment includes administering a composition that includes one or more agents to decrease the expression and/or activity of miRNA-124 and one or more agents to alter the activity of miRNA-29 (increase or decrease). Also disclosed are methods of enhancing muscle regeneration, repair, or maintenance in a subject and methods of enhancing α7β1 integrin expression. Methods of prospectively preventing or reducing muscle injury or damage in a subject are also disclosed.

## Claims

### Claim 1

A method, comprising:
administering to a subject with Duchenne muscular dystrophy (DMD) an effective amount of an antisense compound that downregulates miRNA-124 expression, thereby down-regulating miRNA-124 expression in the subject with DMD.

### Claim 2 (depends on 1)

The method of claim 1, wherein the antisense compound is an antisense oligonucleotide, siRNA or ribozyme.

### Claim 3 (depends on 1)

The method of claim 1, wherein the antisense compound downregulates miRNA-124 by decreasing expression of miRNA-124-1, miRNA-124-2, miRNA-124-3, or a combination thereof.

### Claim 4 (depends on 1)

The method of claim 1, further comprising administering MLS-969.

### Claim 5 (depends on 4)

The method of claim 4, wherein the antisense compound that downregulates miRNA-124 and MLS-969 are administered simultaneously.

### Claim 6 (depends on 4)

The method of claim 4, wherein the antisense compound that downregulates miRNA-124 is administered prior to administration of MLS-969.

### Claim 7 (depends on 1)

The method of claim 1, wherein the subject is a human.

### Claim 8 (depends on 1)

The method of claim 1, further comprising diagnosing a subject with DMD by:
detecting expression of at least one microRNA (miR) gene product in a sample obtained from the subject, wherein the at least one miR gene product comprises at least miRNA-124; and
comparing expression of at least one of the miR gene product in the sample obtained from the subject to a control,
wherein altered expression of the at least one miR gene product in the sample obtained from the subject, including at least increased expression in miRNA-124, compared to the control identifies a subject with DMD.

### Claim 9 (depends on 8)

The method of claim 8, wherein the at least one miR gene product comprises miRNA-124 and miRNA-29.

### Claim 10 (depends on 8)

The method of claim 8, wherein altered expression comprises an at least two-fold increase in miRNA-124.

### Claim 11 (depends on 9)

The method of claim 9, wherein altered expression comprises an at least two-fold increase in miRNA-124 and an at least two-fold decrease in miRNA-29.

### Claim 12 (depends on 8)

The method of claim 8, wherein the antisense compound downregulates miRNA-124 by decreasing expression of miRNA-124-1, miRNA-124-2, miRNA-124-3, or a combination thereof.

### Claim 13 (depends on 8)

The method of claim 8, further comprising administering MLS-969.
