Prevention and/or treatment of hearing loss or impairment

Patent metadata

Field	Value
Publication number	US-11679140-B2
Application number	US-202016940010-A
Country	US
Kind code	B2
Filing date	Jul 27, 2020
Priority date	Feb 20, 2015
Publication date	Jun 20, 2023
Grant date	Jun 20, 2023

Abstract

The present invention relates to the use of gasdermin, in particular of gasdermin A, gasdermin B, gasdermin C, gasdermin D, DFNA5 or DFNB59 (or pejvakin), and more particularly pejvakin for modulating cellular redox homeostasis. A particularly preferred use of gasdermin, in particular of gasdermin A, gasdermin B, gasdermin C, gasdermin D, DFNA5 or DFNB59 (or pejvakin), and more particularly pejvakin in the context of the present invention is as an antioxidant. The present invention also concerns a virally-mediated gene therapy for restoring genetically-impaired auditory and vestibular functions in subjects suffering from an Usher syndrome. More precisely, this gene therapy takes advantage of an AAV2/8 vector expressing at least one USH1 gene product, preferably SANS.

First claim

The invention claimed is:

1. A method of gene therapy for Usher syndrome, comprising administering an effective amount of a vector comprising a coding sequence for an USH1 gene product, which is the SANS gene product, to a subject in need thereof.

2. The method of claim 1 , wherein the USH1 gene product is the SANS gene product having the amino acid sequence SEQ ID NO:49.

3. The method of claim 1 , wherein the vector comprises the nucleic acid sequence of SEQ ID NO: 47 and/or SEQ ID NO: 48.

4. The method of claim 1 , wherein the USH1 gene product is the SANS gene product having the amino acid sequence SEQ ID NO:49, and wherein the vector comprises the nucleic acid sequence of SEQ ID NO: 47 and the nucleic acid sequence of SEQ ID NO: 48.

5. The method of claim 1 , wherein the vector is a viral vector.

6. The method of claim 5 , wherein the vector is administered by administering a viral particle comprising the vector to the subject.

7. The method of claim 5 , wherein the vector is selected from the group consisting of lentivirus vectors, adenovirus vectors, and adeno-associated virus (AAV) vectors.

8. The method of claim 7 , wherein the vector is an AAV vector.

9. The method of claim 8 , wherein the vector is an AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, or AAV10 vector.

10. The method of claim 8 , wherein the vector is a AAV2/8 vector.

11. The method of claim 1 , wherein the vector is administered by cochlear injection.

12. The method of claim 1 , wherein administering the effective amount of the vector to the subject rescues auditory function.

13. The method of claim 1 , wherein administering the effective amount of the vector to the subject rescues vestibular defects.

14. The method of claim 1 , wherein the USH1 gene product is expressed in both inner hair cells (IHCs) and outer hair cells (OHCs) of the auditory system of the subject.

15. The method of claim 11 , wherein administering the effective amount of the vector to the subject rescues auditory function.

16. The method of claim 11 , wherein administering the effective amount of the vector to the subject rescues vestibular defects.

17. The method of claim 11 , wherein the USH1 gene product is expressed in both inner hair cells (IHCs) and outer hair cells (OHCs) of the auditory system of the subject.

Assignees

• Pasteur Institut
• Centre Nat Rech Scient
• Univ Sorbonne
• Univ Clermont Auvergne

Inventors

• Petit Christine
• Avan Paul
• Delmaghani Sedigheh
• Defourny Jean
• Aghaie Asadollah
• Safieddine Saaid
• Emptoz Alice

Classifications

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• C12N2710/10021

  Viruses as such, e.g. new isolates, mutants or their genomic sequences · CPC title

• A61K8/64

  Proteins; Peptides; Derivatives or degradation products thereof · CPC title

• A01K2217/075

  inducing loss of function, i.e. knock out · CPC title

• C12N7/00

  Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00) · CPC title