# US 2019/0167761 A1 · Pharmaceutical composition for preventing or treating stress-related disease, including disc1 protein or gene encoding the same

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- Number: US 2019/0167761 A1
- Document ID: US20190167761A1
- Status: Published application
- Kind: A1
- Application number: 16/197,491
- Filed: 2018-11-21
- Published: 2019-06-06
- Earliest claimed: 2017-12-01
- Assignees: Postech Academy-Industry Foundation
- Applicants: Postech Academy-Industry Foundation
- Inventors: Sang Ki PARK; Nhung TRUONG; Sung Jin PARK; Yeong Jun SUH; Cana PARK
- Web page: https://patentgrep.com/patent/US20190167761A1

## CPC

- A61K 38/1709: {from mammals}
- A61K 35/30: Nerves; Brain; Eyes; Corneal cells; Cerebrospinal fluid; Neuronal stem cells; Neuronal precursor cells; Glial cells; Oligodendrocytes; Schwann cells; Astroglia; Astrocytes; Choroid plexus; Spinal cord tissue
- A61P 25/22: Anxiolytics
- A61P 25/24: Antidepressants
- C07K 14/47: from mammals
- C12Q 1/025: {for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics (antimicrobial activity C12Q1/18)}
- G01N 33/5008: {for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics}
- G01N 33/6896: {Neurological disorders, e.g. Alzheimer's disease}
- A61K 48/005: {characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered}
- G01N 2500/10: involving cells
- G01N 2800/30: Psychoses; Psychiatry
- 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
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- 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

Provided herein are a pharmaceutical composition for preventing or treating a stress-related disease, which includes the DISC1 protein or a gene encoding the DISC protein, and a method of screening a material for preventing or treating the stress-related disease. As a result of studying the association between DISC1 and psychological stress, the inventors of the present disclosure verified the function of DISC1 in downregulating ER-mitochondria Ca2+ transfer induced by stress hormone-mediated oxidative stress by competitively inhibiting the binding of IP3 to inositol 1,4,5-trisphosphate (IP3) receptor type1 (IP3R1) by binding to the IP3R1 at the MAM, and an acting site of DISC1, and this provides a model of intracellular calcium response to physiological stress, and DISC1, a stress modulating substance, and the model may be usefully used in related fields for the prevention and treatment of stress-related diseases.

## Claims

### Claim 1

A method for treating a stress-related disease, comprising:
administering to a subject in need thereof an effective amount of disrupted in schizophrenia 1 (DISC1) protein or a gene encoding the DISC1 protein.

### Claim 2 (depends on 1)

The method according to claim 1, wherein the stress-related disease is selected from the group consisting of sleep disorders, depression, adaptive disorders, eating disorders, and anxiety disorders.

### Claim 3 (depends on 1)

The method according to claim 1, wherein the gene is inserted into a plasmid expression vector or a viral vector.

### Claim 4 (depends on 1)

The method according to claim 1, wherein the DISC1 protein regulates endoplasmic reticulum-mitochondria Ca2+ transfer induced by stress hormone-mediated oxidative stress at a mitochondria-associated endoplasmic reticulum membrane (MAM).

### Claim 5 (depends on 4)

The method according to claim 4, wherein the DISC 1 protein regulates Ca2+ transfer by competitively inhibiting binding of IP3 to inositol 1,4,5-trisphosphate (IP3) receptor type1 (IP3R1) by binding to the IP3R1 at the MAM.

### Claim 6 (depends on 4)

The method according to claim 4, wherein the stress hormone comprises a glucocorticoid.

### Claim 7

A method for screening a material for preventing or treating a stress-related disease, the method comprising:
(a) treating cells expressing a disrupted in schizophrenia 1 (DISC1) protein or a gene encoding the DISC1 protein with a candidate material in vitro;
(b) measuring an expression level or activity of the DISC1 protein in the cells; and
(c) selecting, as a material for preventing or treating a stress-related disease, a material that increases the expression level or activity of the DISC1 protein as compared to a group that is not treated with the candidate material.

### Claim 8 (depends on 7)

The method of claim 7, wherein the cells comprise neurons.

### Claim 9 (depends on 7)

The method according to claim 7, wherein the candidate material is selected from the group consisting of a compound, a microorganism culture or extract, a natural extract, a nucleic acid, and a peptide.

### Claim 10 (depends on 9)

The method according to claim 9, wherein the nucleic acid is selected from the group consisting of siRNA, shRNA, microRNA, antisense RNA, an aptamer, a locked nucleic acid (LNA), a peptide nucleic acid (PNA), and a morpholino.

### Claim 11 (depends on 7)

The method according to claim 7, wherein in the measuring, the expression level is measured using one or more methods selected from the group consisting of western blotting, radioimmunoassay (RIA), radioimmunodiffusion, enzyme-linked immunosorbent assay (ELISA), immunoprecipitation, flow cytometry, immunofluorescence, Ouchterlony double immunodiffusion, a complement fixation assay, and a protein chip.

### Claim 12 (depends on 7)

The method according to claim 7, wherein in the measuring, the activity is measured by measuring a degree to which the DISC1 protein decreases endoplasmic reticulum-mitochondria Ca2+ transfer by competitively inhibiting binding of IP3 to IP3R1 by binding to the IP3R1 at the MAM.
