ArticleOtology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology2024
A Selection Protocol to Identify Therapeutics to Target NLRP3-Associated Sensory Hearing Loss.
Article in Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- Auditory and Vestibular Involvement in Congenital Cytomegalovirus Infection.Pathogens (Basel, Switzerland) · 2024Review
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Authors and funding
6 authors.
Funding
Abstract
objectiveWe propose a selection process to identify a small molecule inhibitor to treat NLRP3-associated sensory hearing loss.
backgroundThe NLRP3 inflammasome is an innate immune sensor and present in monocytes and macrophages. Once the inflammasome is activated, a cleavage cascade is initiated leading to the release of proinflammatory cytokines IL-1β and IL-18. The NLRP3 inflammasome has been implicated in many causes of hearing loss, including autoimmune disease, tumors, and chronic suppurative otitis media. Although the target has been identified, there is a lack of available therapeutics to treat NLRP3-associated hearing loss.
methodsWe created a target product profile with specific characteristics that are required for a compound to treat sensory hearing loss. We then looked at available small molecule NLRP3 inhibitors at different stages of development and selected compounds that fit that profile best. Those compounds were then tested for cell toxicity in MTT assays to determine the dosage to be used for efficacy testing. We tested efficacy of a known NLRP3 inhibitor, MCC950, in a proof-of-concept screen on reporter monocytes.
resultsSix compounds were selected that fulfilled our selection criteria for further testing. We found the maximum tolerated dose for each of those compounds that will be used for further efficacy testing. The proof-of-concept efficacy screen on reporter monocytes confirmed that those cells can be used for further efficacy testing.
conclusionOur selection process and preliminary results provide a promising concept to develop small molecule NLRP3 inhibitors to treat sensory hearing loss.
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