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Late-Breaking Scientific Oral Presentations

Otology/Neurotology

Session: Late-Breaking Scientific Orals: Otology and Neurotology

SPI-1005 (Ebselen) Reduces Low Frequency Hearing Loss After Cochlear Implantation in Guinea Pigs

Sunday, September 29, 2024

2:48 PM – 2:54 PM EDT

Location: MBCC, 222

Disclosure(s):

Jonathan Kil, MD:

faculty for this accredited education activity has no relationship(s) with ineligible companies to disclose.

Rende Gu, MD:

faculty for this accredited education activity has no relationship(s) with ineligible companies to disclose.

Introduction: SPI-1005 (ebselen) is a novel anti-inflammatory that could improve residual low frequency hearing following cochlear implantation.

Methods: Study goals included developing a novel implantable formulation of ebselen (silicone) that improves low frequency hearing in adult guinea pigs and was conducted from April 2022 to June 2024 under IACUC approval. A series of in vitro and in vivo tests assayed ebselen release (IVRT), acute ototoxicity (cochlear cultures), hearing sensitivity (ABR), and chronic ototoxicity (histopathology). In total, 60 neonatal mice cochlear cultures were run for 3-7 days in the presence of 30% ebselen strips. A total of 24 guinea pigs (GPs) were surgically implanted (unilaterally) with a 0.75 mm silicone strip containing ebselen at 0% (control) or 30% (active) concentration into the scala tympani via the RWN. GPs were followed for 180 days and re-assessed at 1-week, 1, 2, 3, and 6-months post-implantation. ABR threshold shifts in the implanted left ear were subtracted from the threshold shift in the un-implanted right ear and that difference was compared between control and active groups at 4, 8, 16, 24, and 32 kHz over 6 months. Cochlear histopathology involved immunofluorescence to determine the length of hair cell loss (mm) in implanted cochlea.

Results: IVRT showed that 30% strips elute ebselen over a 90-180-day period. Mouse cochlear cultures showed no hair cell loss after 3-7 days of exposure to ebselen strips. In GPs, ABR threshold shifts were highest at 1-week (20-35 dB) and decreased steadily at 1, 2, and 3-months (5-10 dB) post-implantation. At 6-months, threshold shifts increased in both active and control guinea pigs. Ebselen implanted GPs showed improvements at 4 kHz (15-20 dB) at 2 and 6 months when compared to controls (p-values < 0.05). Hair cell loss was limited to the site of cochlear implantation (2 mm) and there was no significant difference between actives and controls.

Conclusions: These preclinical data show that a novel silicone formulation of ebselen can improve low frequency hearing when compared to controls and support the combination of ebselen with a cochlear implant to improve residual hearing.

Presenting Author(s)

Jonathan Kil, MD

CMO
Sound Pharmaceuticals
Seattle, WA, United States

Disclosure(s):
faculty for this accredited education activity has no relationship(s) with ineligible companies to disclose.

Co-Author(s)

Jonathan Kil, MD

CMO
Sound Pharmaceuticals
Seattle, WA, United States

Disclosure(s):
faculty for this accredited education activity has no relationship(s) with ineligible companies to disclose.

Senior Author(s)

Jonathan Kil, MD

CMO
Sound Pharmaceuticals
Seattle, WA, United States

Disclosure(s):
faculty for this accredited education activity has no relationship(s) with ineligible companies to disclose.

Co-Author(s)

RG

Rende Gu, MD

Scientist
Sound Pharmaceuticals, Inc.
Seattle, WA, United States

Disclosure(s):
faculty for this accredited education activity has no relationship(s) with ineligible companies to disclose.
AJ

Annie Jia

Research Fellow
Sound Pharmaceuticals, Inc.
Seattle, Washington, United States

Disclosure information not submitted.
GW

G. M. Wall, PhD

VP Pharmaceutical Development
Sound Pharmaceuticals, Inc.
Seattle, WA, United States

Disclosure information not submitted.