Methods and pharmaceutical compositions for the treatment of post-operative cognitive dysfunction

Patent metadata

Field	Value
Publication number	US-11484577-B2
Application number	US-201716077949-A
Country	US
Kind code	B2
Filing date	Feb 14, 2017
Priority date	Feb 15, 2016
Publication date	Nov 1, 2022
Grant date	Nov 1, 2022

Abstract

The present invention relates to methods and pharmaceutical compositions for the treatment of post-operative cognitive dysfunction. In particular, the present invention relates to a method of treating post-operative cognitive dysfunction in a subject in need thereof comprising administering to the subject a therapeutically effective amount of an APJ receptor agonist.

First claim

The invention claimed is:

1. A method of treating post-operative cognitive dysfunction in a subject in need thereof comprising administering to the subject a therapeutically effective amount of an APJ receptor agonist, wherein the APJ receptor agonist is apelin-13;
wherein the APJ receptor agonist is administered perioperatively;
wherein cognitive impairment of memory, attention, learning and/or speed of information processing caused by surgery is reduced or ameliorated; and
and wherein the cognitive impairment is measured prior to and/or following the surgery by performing at least one neuropsychological test to test a function selected from the group consisting of verbal comprehension, perceptual organization, executive function, abstraction, problem solving, cognitive flexibility, visual tracking, game performance, psychomotor performance, psychomotor speed, digital symbol substitution, processing speed, dot-connection, flicker-fusion, simple reaction time, choice reaction time and perceptive accuracy.

2. The method of claim 1 wherein the subject is determined to be at risk for post-operative cognitive dysfunction.

3. The method of claim 1 wherein the subject is diagnosed with or indicated to have impairment in cognition.

4. The method of claim 1 wherein the post-operative cognitive dysfunction is cognitive impairment experienced after surgery selected from the group consisting of abdominal surgery, bench surgery, cardiac surgery, cerebral surgery, cineplastic surgery, cosmetic surgery, dentofacial surgery, neurological surgery, oral surgery, orthopedic surgery, pelvic surgery, plastic surgery, rectal surgery, urological surgery, vascular surgery, and otolaryngology surgery.

5. The method of claim 1 wherein the APJ receptor agonist is administered concomitantly or sequentially with an anesthetic to the subject.

6. The method of claim 5 wherein anesthetic is selected from the group consisting of diethyl ether, methoxypropane, vinyl ether, halogenated ethers, haloalkanes, trichloroethylene, cyclopropane, ethylene, nitrous oxide, sevoflurane, xenon, hexafluoro-t-butyl-difluoromethyl ether, deuterated isoflurane, a deutered analogue of methoxyflurane, and deutered sevoflurane.

7. The method of claim 1 wherein APJ receptor agonist is selected from the group consisting of small organic molecules, aptamers, antibodies and polypeptides.

8. The method of claim 1 , wherein the APJ receptor agonist is administered within six hours prior to administration of an anesthetic and/or within six hours following administration of an anesthetic.

9. The method of claim 4 , wherein
the abdominal surgery is surgery of the abdominal viscera;
the bench surgery is surgery performed on an organ that has been removed from the body;
the cineplastic surgery is surgery to create a tunnel through a muscle adjacent to a stump of an amputated limb to permit use of the muscle in operating a prosthesis;
the cosmetic surgery is surgery to improve the subject's appearance by plastic restoration, correction or removal of blemishes;
the dentofacial surgery is surgery to correct defects of the face and structures of the mouth;
the neurological surgery is surgery involving the peripheral or central nervous system;
the pelvic surgery is obstetrical and/or gynaecological surgery;
the oral surgery is surgery to correct defects of the mouth, jaws and associated structures;
the orthopedic surgery is hip replacement;
the plastic surgery is surgery involving restoration, reconstruction, correction or improvement in shape and appearance of body structures that are defective, damaged or misshapened by injury, disease, or growth and development;
the urological surgery is surgery of the male genitourinary system; and
the otolaryngology surgery is surgery of the ears, nose, throat or related structures.

10. The method of claim 6 , wherein
the halogenated ether is desflurane, enflurane, halothane, isoflurane, or methoxyflurane; and
the haloalkane is chloroform or halothane.

11. A method of treating or inhibiting post-operative cognitive dysfunction in a subject in need thereof, comprising
administering to the subject a therapeutically effective amount of an APJ receptor agonist, wherein the APJ receptor agonist is apelin-13;
wherein the therapeutically effective amount of the APJ receptor agonist is sufficient to reduce or ameliorate a cognitive impairment of memory, attention, learning and/or speed of information processing caused by an anesthetic administered for a surgery; and
wherein the cognitive impairment is measured prior to and/or following the surgery by performing at least one neuropsychological test to test a function selected from the group consisting of verbal comprehension, perceptual organization, executive function, abstraction, problem solving, cognitive flexibility, visual tracking, game performance, psychomotor performance, psychomotor speed, digital symbol substitution, processing speed, dot-connection, flicker-fusion, simple reaction time, choice reaction time and perceptive accuracy.

12. The method of claim 11 , wherein the APJ receptor agonist is administered within six hours prior to and/or within six hours following administration of the anesthetic.

Assignees

• Inst Nat Sante Rech Med
• Univ Toulouse 3 Paul Sabatier
• Ct Hospitalier Universitaire Toulouse

Inventors

• Valet Philippe
• Dray Cedric
• Minville Vincent
• Frances Bernard
• Labaste Francois
• Vinel Claire

Classifications

• A61K31/015

  carbocyclic · CPC title

• A61K31/08

  acyclic, e.g. paraformaldehyde · CPC title

• A61K38/1709

  from mammals · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title