Abstract: This invention relates to methods for treating hearing loss associated with loss of cochlear hair cells, e.g., caused by noise exposure, using certain gamma secretase inhibitors, in post-neonatal animals, e.g., adolescents and adults.

Abstract: The present disclosure provides compositions and methods for treating subjects at risk for or with sensorineural hearing loss. Such compositions and methods include modulating the epigenetic status of the cell, or rate of protein degradation, to increase expression and/or levels of Atoh1 protein.

Abstract: Methods for generating cells of the inner ear, e.g., hair cells and supporting cells, from stem cells, e.g., mesenchymal stem cells, are provided, as well as compositions including the inner ear cells. Methods for the therapeutic use of the inner ear cells for the treatment of hearing loss are also described.

Abstract: This invention generally provides compounds, pharmaceutical compositions, and methods for their use, which include methods that result in increased expression in an Atoh1 gene (e.g., Hath1) in a biological cell. More specifically, the invention relates to the treatment of diseases and/or disorders that would benefit from increased Atoh1 expression, e.g., a hearing impairment or imbalance disorder associated with a loss of auditory hair cells, or a disorder associated with abnormal cellular proliferation.

Abstract: The present disclosure provides compositions and methods for treating subjects at risk for or with sensorineural hearing loss. Such compositions and methods include modulating the epigenetic status of the cell, or rate of protein degradation, to increase expression and/or levels of Atoh1 protein.

Abstract: This invention relates to uses of activators of ErbB3/HER3 in expanding inner ear cells and restoring hearing loss.

Abstract: This invention relates to methods for promoting reinnervation of auditory hair cells, specifically, by inhibiting Repulsive Guidance Molecule a (RGMa), a repulsive axonal guidance molecule that is expressed in the cochlea, or its receptor, neogenin.

Abstract: The present invention provides the following compounds, or pharmaceutically acceptable salts thereof, and pharmaceutical compositions containing said compounds useful as a Notch pathway signaling inhibitor for the treatment of named cancers, sensorineural hearing loss caused by auditory hair cell loss, and inducing auditory hair cell generation.

Abstract: This invention generally provides compounds, pharmaceutical compositions, and methods for their use, which include methods that result in increased expression in an Atoh1 gene (e.g., Hath1) in a biological cell. More specifically, the invention relates to the treatment of diseases and/or disorders that would benefit from increased Atoh1 expression, e.g., a hearing impairment or imbalance disorder associated with a loss of auditory hair cells, or a disorder associated with abnormal cellular proliferation.

Abstract: Methods for treating hearing loss that include administering an inhibitor, e.g., a small molecule inhibitor, of casein kinase 1, preferably in combination with a treatment that stimulates Atoh1 gene expression, e.g., a gamma-secretase inhibitor, an Atoh1 stimulatory compound, or a GSK-3-beta inhibitor.

Abstract: Methods for generating cells of the inner ear, e.g., hair cells and supporting cells, from stem cells, e.g., mesenchymal stem cells, are provided, as well as compositions including the inner ear cells. Methods for the therapeutic use of the inner ear cells for the treatment of hearing loss are also described.

Abstract: The present disclosure provides compositions and methods for treating subjects at risk for or with sensorineural hearing loss by modulating the rate of Atoh1 protein degradation to increase levels of Atoh1 protein.

Abstract: This disclosure relates to methods and compositions for modulating (e.g., increasing) Atoh1 activity (e.g., biological activity) and/or expression (e.g., transcription and/or translation) in vivo and/or in vitro, e.g., in a biological cell and/or in a subject. The methods and compositions described herein can be used in the treatment of diseases and/or disorders that would benefit from increased Atoh1 expression in a biological cell.

Abstract: This invention relates to drug conjugates useful for localized treatment of diseases or disorders of the middle ear and/or inner ear. Methods of treating diseases or disorders of the middle ear and/or inner ear, pharmaceutical compositions comprising the conjugates, and methods of inhibiting a Tropomyosin receptor kinase are also provided.

Abstract: Methods of treating or reducing the risk of developing hidden hearing loss by administering a small molecule Trk agonists (e.g., amitriptyline, imipramine, LM 22A4 (N,N?,N?Tris(2-hydroxyethyl)-1,3,5-benzenetricarboxamide), 7, 8-dihydroxyflavone (DHF), 7,8,3?-Trihydroxyflavone (THF), Mab2256, neurotrophin-4 (NT-4), neurotrophin-3 (NT-3), brain derived neurotrophic factor (BDNF), nerve growth factor (NGF), N-acetylserotonin, N-[2-(5-Hydroxy-1H-indol-3-yl)ethyl]-2-oxo-3-piperidinecarboxamide (HIOC), deoxygedunin, LM-22A4, or tricyclic dimeric peptide 6 (TDP6)).

Abstract: This disclosure relates to methods for expanding inner ear supporting cells (e.g., Lgr5+ inner ear supporting cells) and differentiating inner ear supporting cells (e.g., Lgr5+ inner ear supporting cells) to inner ear hair cells (e.g., atonal homolog 1 (Atoh1)+ inner ear hair cells) and the use of the inner hear supporting cells and hair cells, e.g., for identifying candidate therapeutic compounds for the treatment of hearing loss and balance loss. Additionally, the methods described herein can be used in the treatment of a subject having hearing loss and balance loss that would benefit from increased proliferation and differentiation of inner ear supporting cells (e.g., Lgr5+ inner ear supporting cells).

Abstract: This invention relates to methods for treating hearing loss associated with loss of cochlear hair cells, e.g., caused by noise exposure, using certain gamma secretase inhibitors, in post-neonatal animals, e.g., adolescents and adults.

Abstract: This disclosure relates to methods and compositions for modulating (e.g., increasing) Atoh1 activity (e.g., biological activity) and/or expression (e.g., transcription and/or translation) in vivo and/or in vitro, e.g., in a biological cell and/or in a subject. The methods and compositions described herein can be used in the treatment of diseases and/or disorders that would benefit from increased Atoh1 expression in a biological cell.

Abstract: Methods for generating cells of the inner ear, e.g., hair cells and supporting cells, from stem cells, e.g., mesenchymal stem cells, are provided, as well as compositions including the inner ear cells. Methods for the therapeutic use of the inner ear cells for the treatment of hearing loss are also described.

Abstract: The present invention provides the following compounds, or pharmaceutically acceptable salts thereof, and pharmaceutical compositions containing said compounds useful as a Notch pathway signaling inhibitor for the treatment of named cancers, sensorineural hearing loss caused by auditory hair cell loss, and inducing auditory hair cell generation.