ArticleNature chemical biology2016
A small molecule mitigates hearing loss in a mouse model of Usher syndrome III.
Article in Nature chemical biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06592131 (First-in-Human Phase-1, Randomised, Double-Blinded, Placebo Controlled Study to Assess Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Doses, As Well As a Food Effect Study, of BF844 When Administered Orally to Healthy Adult Participants), which is not on this map. Cited by 33 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
First-in-Human Phase-1, Randomised, Double-Blinded, Placebo Controlled Study to Assess Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Doses, As Well As a Food Effect Study, of BF844 When Administered Orally to Healthy Adult Participants
Who cites it
33 citing papers in PubMed, 45 citations in OpenAlex.
- The ubiquitin-proteasome system and proteostasis in the cochlea and sensorineural hearing disorders.Molecular biomedicine · 2026Review
- Small Molecule Therapeutic Approaches With a Greater Focus on Hearing Loss: A Review.Health science reports · 2026Article
- Article
- A Tetrazine-Based Synthesis for Accessing Underutilized Aza-Indole Analogues.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Current approaches for Usher syndrome disease models and developing therapies.Frontiers in cell and developmental biology · 2025Review
- A rare transcript homozygous variants in CLRN1(USH3A) causes Usher syndrome type 3 in a Chinese family.Orphanet journal of rare diseases · 2024Article
- Extracellular vesicles for developing targeted hearing loss therapy.Journal of controlled release : official journal of the Controlled Release Society · 2024Review
- Review
- Usher syndrome IIIA: a review of the disorder and preclinical research advances in therapeutic approaches.Human genetics · 2022Review
- A small molecule high throughput screening platform to profile conformational properties of nascent, ribosome-bound proteins.Scientific reports · 2022Article
- Retinal Gene Therapy for Usher Syndrome: Current Developments, Challenges, and Perspectives.International ophthalmology clinics · 2021Article
- Usher Syndrome in the Inner Ear: Etiologies and Advances in Gene Therapy.International journal of molecular sciences · 2021Review
- Congenital Deafness and Recent Advances Towards Restoring Hearing Loss.Current protocols · 2021Article
- Modulation of protein fate decision by small molecules: targeting molecular chaperone machinery.Acta pharmaceutica Sinica. B · 2020Review
- Fetal gene therapy and pharmacotherapy to treat congenital hearing loss and vestibular dysfunction.Hearing research · 2020Review
- Novel Mutations inGenes · 2020Article
- Fetal antisense oligonucleotide therapy for congenital deafness and vestibular dysfunction.Nucleic acids research · 2020Article
- Usher Syndrome: Genetics and Molecular Links of Hearing Loss and Directions for Therapy.Frontiers in genetics · 2020Review
- Unconventional secretory pathway activation restores hair cell mechanotransduction in an USH3A model.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Folding and Misfolding of Human Membrane Proteins in Health and Disease: From Single Molecules to Cellular Proteostasis.Chemical reviews · 2019Article
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21 authors at 5 institutions in 4 countries.
Funding
Abstract
Usher syndrome type III (USH3), characterized by progressive deafness, variable balance disorder and blindness, is caused by destabilizing mutations in the gene encoding the clarin-1 (CLRN1) protein. Here we report a new strategy to mitigate hearing loss associated with a common USH3 mutation CLRN1(N48K) that involves cell-based high-throughput screening of small molecules capable of stabilizing CLRN1(N48K), followed by a secondary screening to eliminate general proteasome inhibitors, and finally an iterative process to optimize structure-activity relationships. This resulted in the identification of BioFocus 844 (BF844). To test the efficacy of BF844, we developed a mouse model that mimicked the progressive hearing loss associated with USH3. BF844 effectively attenuated progressive hearing loss and prevented deafness in this model. Because the CLRN1(N48K) mutation causes both hearing and vision loss, BF844 could in principle prevent both sensory deficiencies in patients with USH3. Moreover, the strategy described here could help identify drugs for other protein-destabilizing monogenic disorders.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.