Methods of treating, inhibiting and/or preventing an auditory impairment

Patent metadata

Field	Value
Publication number	US-10124062-B2
Application number	US-201715444147-A
Country	US
Kind code	B2
Filing date	Feb 27, 2017
Priority date	Feb 26, 2016
Publication date	Nov 13, 2018
Grant date	Nov 13, 2018

Abstract

The present invention provides methods of treating an auditory impairment associated with outer hair cells of the cochlea in a subject. The method may comprise administering to said subject an effective amount of a composition comprising, as an active agent, an oligonucleotide sequence having a portion of a mammalian telomere sequence so as to reduce the auditory impairment thereby treating the auditory impairment in the subject.

First claim

What is claimed is:

1. A method of inhibiting or treating an auditory impairment associated with outer hair cells of the cochlea in a subject comprising administering to said subject an effective amount of a composition comprising, as an active agent, an oligonucleotide sequence having a portion of a mammalian telomere sequence or a variant of a mammalian telomere sequence so as to preserve or restore outer hair cell function, preserve or restore retrocochlear function, and/or improve DNA repair, thereby inhibiting or treating the auditory impairment in the subject.

2. The method of claim 1 , wherein the composition increases activation of p53 without an increase in p53 total protein concentration sufficient to induce apoptosis of cochlear outer hair cells.

3. The method of claim 1 , wherein the auditory impairment is selected from a group consisting of temporary hearing loss, permanent hearing loss, sensory hearing loss, sensorineural hearing loss, tinnitus, loudness recruitment, hyperacusis, diplacusis and speech intelligibility deficits.

4. The method of claim 1 , wherein the oligonucleotide sequence is isolated from a telomere.

5. The method of claim 1 , wherein the oligonucleotide is a modified oligonucleotide.

6. The method of claim 1 , wherein the composition is administered topically, by injection, as a swab, as a patch, as a droplet, as a stream, as an aerosol, by an implant, by a device generating a voltage potential, by a nanoparticle, by a projectile, in an aqueous solution, in saline solution, in a non-aqueous solution, in glycerol, as a solid, as a fluid, as a micelle, as a salt, as a complex with a metal, as a complex with a counter ion, as a complex with a lipid, or as a conjugate with a cell targeting agent.

7. The method of claim 1 , wherein the oligonucleotide having a portion of a mammalian telomere sequence that is 100% homologous to a mammalian telomere sequence comprising direct repeats of a hexanucleotide sequence (TTAGGG) is selected from the group consisting of: GTTAGGGTT, TTAGGGTTA, GGGTTAGGG, GTTAGGGTTAG (SEQ ID NO. 1), GTTAGGGTTAGGGTT (SEQ ID NO. 5), and GTTAGGGTTAGGGTTA (SEQ ID NO. 4).

Assignees

• The Dept Of Veterans Affairs
• Us Veterans Affairs

Inventors

• Guthrie O'Neil W

Classifications

• C12N15/11

  DNA or RNA fragments; Modified forms thereof (DNA or RNA not used in recombinant technology, C07H21/00); {Non-coding nucleic acids having a biological activity} · CPC title

• A61K45/06 Primary

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K31/713

  Double-stranded nucleic acids or oligonucleotides · CPC title