Massachusetts Eye and Ear Infirmary

The Brigham and Women's Hospital, Inc.

University of Southern California

Eli Lilly and Company

Decibel Therapeutics, Inc.

Audion Therapeutics

Albert Edge

Judith Kempfle

Gregory D Cuny

Lixin Qiao

Marcie A Glicksman

Sang-Jun Jeon

Kathleen Seyb

Michael J McKenna

Dunia Abdul-Aziz

Stefan Heller

Masato Fujioka

Hideyuki Okano

Boris A Kashemirov

Konstantina Stankovic

William Sewell

Kunio Mizutari

Kim Nguyen

David Jung

Shyan-Yuan Kao

Woo Seok Kang

Yenfu Cheng

Philip Arthur Hipskind

Charles E McKenna

Gaiying Zhao

Bharvin Kumar Patel

Shuting Sun

Fuxin Shi

Agnieszka Czechowicz

Daniel J Lee

Julia Marie Clay

Aaron David Wrobleski

Huawei Li

Xiankai Meng

Charles E Mckenna

Michael Venuti

Helmuth Hendrikus Gerardus Van Es

John C Gill

Yen-Fu Cheng

Hideyuk Okano

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.

Phosphonate-drug conjugates

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.

Sensorineural hair cell differentiation

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.

Treatment of hearing loss by inhibition of casein kinase 1

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.

Treating hearing loss

The invention relates to multimodal, e.g., bimodal, hybrid cochlear implants that provide both optical (optogenetic) as well as electrical stimulation to enhance sensitivity.

Bimodal hybrid cochlear implants

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.

Generation of inner ear cells

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).

Expansion and differentiation of inner ear supporting cells and methods of use thereof

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.

Increasing ATOH1 life to drive sensorineural hair cell differentiation

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.

Compounds that enhance Atoh1 expression

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.

Methods for promoting reinnervation of auditory hair cells

Growing community of inventors

Brookline, MA, United States of America

Albert Edge