Prevention and/or treatment of hearing loss or impairment

Patent metadata

Field	Value
Publication number	US-10751385-B2
Application number	US-201615551096-A
Country	US
Kind code	B2
Filing date	Feb 19, 2016
Priority date	Feb 20, 2015
Publication date	Aug 25, 2020
Grant date	Aug 25, 2020

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 for modulating cellular redox homeostasis, comprising administering a Pejvakin of SEQ ID NO:1 or a homologous sequence having an amino acid sequence at least 70% identical to SEQ ID NO:1 to a patient suffering from an age-related disease selected from Parkinson's disease (PD), Alzheimer's disease (AD), Familial Amyotrophic Lateral Sclerosis (FALS), age-related macular degeneration (ARMD), type 2 diabetes, atherosclerosis, arthritis, cataracts, osteoporosis, hypertension, skin aging, skin pigmentation, and cardiovascular diseases; a patient suffering from a peroxisomal disorder leading to ROS production, or a patient suffering from a mitochondrial disorder leading to ROS production;
wherein administering the Pejvakin of SEQ ID NO:1 or the homologous sequence having an amino acid sequence at least 70% identical to SEQ ID NO:1 to the patient thereby treats the age-related disease selected from Parkinson's disease (PD), Alzheimer's disease (AD), Familial Amyotrophic Lateral Sclerosis (FALS), age-related macular degeneration (ARMD), type 2 diabetes, atherosclerosis, arthritis, cataracts, osteoporosis, hypertension, skin aging, skin pigmentation, and cardiovascular diseases, treats the peroxisomal disorder leading to ROS production, or treats the mitochondrial disorder leading to ROS production.

2. The method of claim 1 , wherein administering the Pejvakin of SEQ ID NO:1 or the homologous sequence having an amino acid sequence at least 70% identical to SEQ ID NO:1 to the patient alleviates ROS-induced cellular damage in the patient.

3. The method of claim 1 , wherein the patient normally expresses Pejvakin.

4. The method of claim 1 , wherein the Pejvakin of SEQ ID NO:1 or the homologous sequence having an amino acid sequence at least 70% identical to SEQ ID NO:1 is administered to the patient by a method comprising administering a vector encoding the Pejvakin polypeptide to the patient.

5. The method of claim 1 , wherein the patient suffers from an age-related disease selected from Parkinson's disease (PD), Alzheimer's disease (AD), Familial Amyotrophic Lateral Sclerosis (FALS), age-related macular degeneration (ARMD), type 2 diabetes, atherosclerosis, arthritis, cataracts, osteoporosis, hypertension, skin aging, skin pigmentation, and cardiovascular diseases.

6. The method of claim 1 , wherein the patient suffers from a peroxisomal disorder leading to ROS production.

7. The method of claim 1 , wherein the patient suffers from a mitochondrial disorder leading to ROS production.

Assignees

• Pasteur Institut
• Centre National De La Recherche Scient (Cnrs)
• Sorbonne Université
• Université Clermont Auvergne

Inventors

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

Classifications

• A01K2267/0306

  Animal model for genetic diseases · CPC title

• A61K35/761

  Adenovirus · CPC title

• A61K48/0075

  characterised by an aspect of the delivery route, e.g. oral, subcutaneous · CPC title

• A61K48/00

  Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy · CPC title

• A61K48/005

  characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered · CPC title