# US 10,441,601 B2 · Method for treating schizophrenia

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- Number: US 10,441,601 B2
- Document ID: US10441601B2
- Status: Granted
- Kind: B2
- Application number: 15/740,687
- Filed: 2016-06-30
- Published: 2018-11-08
- Granted: 2019-10-15
- Earliest claimed: 2015-06-30
- Assignees: St. Jude Children's Research Hospital
- Applicants: St. Jude Children's Research Hospital, Inc.
- Inventors: Stanislav S. Zakharenko
- Web page: https://patentgrep.com/patent/US10441601B2

## CPC

- A61K 31/713: Double-stranded nucleic acids or oligonucleotides
- A61K 9/0043: {Nose}
- 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)}
- C12Q 1/6883: for diseases caused by alterations of genetic material
- C12N 15/861: Adenoviral vectors
- C12N 2310/141: MicroRNAs, miRNAs
- C12Q 1/6841: In situ hybridisation
- C12Q 2600/106: Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
- C12Q 2600/178: miRNA, siRNA or ncRNA
- G01N 2800/302: Schizophrenia
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The invention is directed to a method for treating the 22q11 deletion syndrome (22q11 DS) and schizophrenia (SCZ) by replenishment of decreased levels of miR-338-3p in thalamic neurons.

## Claims

### Claim 1

A method for treatment of schizophrenia or 22q11 deletion syndrome in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of (i) miR-338-3p or a mimic or a functional derivative thereof, or (ii) a vector expressing said miR-338-3p or mimic or functional derivative thereof, or (iii) an agent capable of increasing the level or activity of miR-338-3p, wherein the miR-338-3p or mimic or derivative thereof comprises the sequence UCCAGCAUCAGUGAUUUUGUUG (SEQ ID NO: 1).

### Claim 2 (depends on 1)

The method of claim 1, wherein the treatment of schizophrenia results in treatment of a positive symptom of schizophrenia in the subject, wherein the positive symptom of schizophrenia is selected from the group consisting of hallucinations, delusions, disorganized thought, and psychosis.

### Claim 3 (depends on 1)

The method of claim 1, wherein the miR-338-3p or mimic or derivative thereof consists of the sequence UCCAGCAUCAGUGAUUUUGUUG (SEQ ID NO: 1).

### Claim 4 (depends on 1)

The method of claim 1, wherein the administration is systemic, intranasal or targeted to the thalamus.

### Claim 5 (depends on 1)

The method of claim 1, wherein the administration results in an increase in the level of miR-338-3p in thalamic neurons of the subject to the level found in healthy subjects.

### Claim 6 (depends on 1)

The method of claim 1, wherein the administration results in a decrease in sensitivity of thalamic neurons of the subject to an antipsychotic agent.

### Claim 7 (depends on 1)

The method of claim 1, wherein the subject has a decreased level of miR-338-3p in thalamic neurons as compared to a control, wherein the control is a predetermined standard, or the level of miR-338-3p in thalamic neurons of a healthy age- and gender-matched subject or an average value for several such subjects.

### Claim 8 (depends on 1)

The method of claim 1, further comprising determining the level of miR-338-3p in thalamic neurons or a bodily fluid sample obtained from the subject.

### Claim 9 (depends on 8)

The method of claim 8, wherein the bodily fluid is selected from the group consisting of blood, urine, saliva, and cerebrospinal fluid (CSF).

### Claim 10 (depends on 8)

The method of claim 8, wherein the level of miR-338-3p is determined prior to the administration of the treatment.

### Claim 11 (depends on 8)

The method of claim 8, wherein the level of miR-338-3p is determined both prior and after the administration of the treatment.