Local cochlear application of statins for stimulating neurite regrowth in the cochlea

Patent metadata

Field	Value
Publication number	US-9517233-B2
Application number	US-201514875637-A
Country	US
Kind code	B2
Filing date	Oct 5, 2015
Priority date	Dec 21, 2012
Publication date	Dec 13, 2016
Grant date	Dec 13, 2016

Abstract

Statin compositions are disclosed for stimulating neurite growth from spiral ganglion neurons in the inner ear, as well as methods and kits for preventing damage to or treating damage of auditory neurons and/or hair cells of the cochlea following acoustic or toxic insult. An exemplary statin for these methods and kits includes Pitavastatin having the compound formula (VIII):

First claim

We claim:

1. A method of stimulating neurite growth from spiral ganglion neurons in an inner ear, comprising: contacting a neurite with a statin, or a pharmaceutically acceptable salt thereof, wherein the statin comprises a compound selected from a group consisting of compounds having formulas (II)-(VIII):

or a combination thereof.

2. The method of claim 1 , wherein the statin comprises a compound having formula (VIII):

3. The method of claim 1 , wherein the contacting step comprises incubating the neurite with a culture medium comprising the statin.

4. The method of claim 2 , wherein the contacting step comprises incubating the neurite with a culture medium comprising the statin.

5. A method of preventing or treating hearing loss in a subject, comprising: administering to the subject a statin or a pharmaceutically acceptable salt thereof, wherein the statin comprises a compound selected from a group consisting of compounds having formulas (II)-(VIII):

or a combination thereof.

6. A method of claim 5 , wherein the statin comprises a compound having formula (VIII):

7. The method of claim 5 , wherein the administering step comprises contacting a cochlea of the subject with a pharmaceutical composition of the statin or a pharmaceutically acceptable salt thereof.

8. The method of claim 6 , wherein the administering step comprises contacting a cochlea of the subject with a pharmaceutical composition of the statin or a pharmaceutically acceptable salt thereof.

9. The method of claim 5 , wherein the subject is a human.

10. The method of claim 6 , wherein the subject is a human.

11. A kit for preventing or treating hearing loss in a subject, comprising:
a statin comprising a compound selected from a group consisting of compounds having formulas (II)-(VIII):

 or a combination thereof; and
instructions for administering to the subject the statin or a pharmaceutically acceptable salt thereof to prevent or treat hearing loss in the subject.

12. The kit of claim 11 , wherein the statin comprises a compound having formula (VIII):

13. The kit of claim 11 , wherein the administering step comprises contacting a cochlea of the subject with a pharmaceutical composition of the statin or a pharmaceutically acceptable salt thereof.

14. The kit of claim 12 , wherein the administering step comprises contacting a cochlea of the subject with a pharmaceutical composition of the statin or a pharmaceutically acceptable salt thereof.

15. The kit of claim 11 , wherein the subject is a human.

16. The kit of claim 12 , wherein the subject is a human.

Assignees

• Univ Northwestern

Inventors

• Whitlon Donna S
• Richter Claus-Peter

Classifications

• A61K31/40

  having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil · CPC title

• A61K31/47 Primary

  Quinolines; Isoquinolines · CPC title

• A61K31/4418

  having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine · CPC title

• C07D213/55

  Acids; Esters · CPC title

• C07D209/24

  with an alkyl or cycloalkyl radical attached to the ring nitrogen atom · CPC title