METHOD OF TREATING PAIN WITH AN ANTIBODY AGAINST NETRIN-4, UNC5B OR NEOGENIN

• US 20180230469A1
• Filed: 04/10/2018
• Published: 08/16/2018
• Est. Priority Date: 08/19/2013
• Status: Active Grant

• Current Assignee: Osaka University
• Original Assignee: Osaka University
• Inventors: YAMASHITA, Toshihide, HAYANO, Yasufumi
• Granted Patent: US 10,640,768 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 29/02 without antiinflammatory effect
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: 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
• CPC Class Codes: C12N 2310/14 interfering N.A.
• CPC Class Codes: C12N 2320/30 Special therapeutic applications
• CPC Class Codes: C12Q 1/68 involving nucleic acids
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: G01N 2500/02 Screening involving studying the effect of compounds C on the interaction between interacting molecules A and B (e.g. A = enzyme and B = substrate for A, or A = receptor and B = ligand for the receptor)
• CPC Class Codes: G01N 2500/10 involving cells
• CPC Class Codes: G01N 2800/2842 Pain, e.g. neuropathic pain, psychogenic pain
• CPC Class Codes: G01N 33/15 Medicinal preparations ; Physical properties thereof, e.g. dissolubility
• CPC Class Codes: G01N 33/6872 Intracellular protein regulatory factors and their receptors, e.g. including ion channels

Abstract

The present invention provides a screening method for pain suppressors, which method is characterized by using netrin-4 and/or a netrin-4 receptor to select a substance capable of inhibiting downstream signaling from netrin-4. According to the screening method of the present invention, pain suppressors useful as a preventive or therapeutic medicine for pain can be identified. The present invention also provides a pharmaceutical composition for prevention or treatment of pain, which composition comprises, as an active ingredient, a substance capable of inhibiting downstream signaling from netrin-4.

Claims

1-14. -14. (canceled)

15. A screening method for pain suppressors, characterized by using netrin-4 and/or a netrin-4 receptor to select a substance capable of inhibiting downstream signaling from netrin-4, the netrin-4 receptor being Unc5B or neogenin.

16. The method according to claim 15, wherein the substance capable of inhibiting downstream signaling from netrin-4 is a substance capable of inhibiting the expression of netrin-4 or a netrin-4 receptor.

17. The method according to claim 15, wherein the substance capable of inhibiting downstream signaling from netrin-4 is a substance capable of inhibiting the interaction between netrin-4 and a netrin-4 receptor.

18. The method according to claim 16, comprising the steps of:

bringing a test substance into contact with cells expressing netrin-4 and/or a netrin-4 receptor;

measuring the expression level of the netrin-4 and/or the netrin-4 receptor in the cells; and

comparing the expression levels of the netrin-4 and/or the netrin-4 receptor between the cells in contact with the test substance and cells not in contact therewith to select a substance capable of reducing the expression level.

19. The method according to claim 17, comprising the steps of:

bringing a test substance into contact with netrin-4 and a netrin-4 receptor;

confirming the interaction between the netrin-4 and the netrin-4 receptor; and

selecting a substance capable of inhibiting the interaction between the netrin-4 and the netrin-4 receptor.

20. A method for prevention or treatment of pain, comprising the step of administering, to a mammal, an effective amount of a nucleic acid capable of inhibiting the expression of netrin-4, Unc5B or neogenin.

21. The method according to claim 20, wherein the nucleic acid is a siRNA composed of nucleotide sequences of SEQ ID NOS:

1 and 2, nucleotide sequences of SEQ ID NOS;

3 and 4, or nucleotide sequences of SEQ ID NOS;

5 and 6 as sense and antisense strands.