(PP701) Oligonucleotide Therapy to Rescue Cochlear Nonlinear Signal Processing

Advances in DNA technology have now provided a means of delivering noncoding DNA into the cochlea in order to improve nonlinear signal processing following noise induced hearing loss.

Summary: Objective/Rationale:  Prescriptive amplification systems (e.g., hearing aids and cochlear implants) have achieved considerable success in improving cochlear sensitivity.  However, even state-of-the-art amplification systems have not achieved consistent success in addressing the loss of cochlear nonlinear signal processing.  The objective of the current series of experiments is to demonstrate that cochlear noise injury can cause a loss in cochlear nonlinear signal processing, but this type of processing can be rescued when a synthetic non-coding oligonucleotide is delivered into the cochlea after cochlear injury. 

Design:   Long-Evans rats were exposed to a traumatic dose of noise, then after the noise exposure they were treated with non-coding oligonucleotides.  Distortion product otoacoustic emission was used to measure nonlinear signal processing over a 2 month period post-noise exposure.  Additional animals were sub-grouped into a noise exposure group, an oligonucleotide group and a control group. 

Results:   The group treated with noncoding oligonucleotides showed depleted nonlinear signal processing immediately after the noise exposure but completely recovered this processing within 2 months post-noise exposure.  However, the noise exposure group demonstrated permanent depletion of nonlinear cochlear signal processing. 

Conclusion: The current research provides the basis for a multifunctional approach to manage hearing loss, where amplification is used to address auditory sensitivity while oligonucleotide therapy is simultaneously used to address auditory nonlinearity.