The universality of fibrosis as an underlying etiology for many voice disorders stems from the reparative response to injury. To date, treatments have been largely unsatisfactory. Acknowledging that healing is complex, we seek to expand our recent findings elucidating one regulatory mechanism underlying repair in the vocal folds. Specifically, we seek increased insight into the transforming growth factor (TGF)-? signaling cascade. Our preliminary data suggest that targeting this pathway, not TGF-? directly, but rather upstream, to be optimal. Smad3, an upstream cytoplasmic signaling protein provides an ideal target for the use of RNA- based therapeutics, specifically small interfering ribonucleic acid (siRNA). However, delivery of siRNA in vivo is complicated by the inherent proteolytic environment. We hypothesize that lipid nanoparticle delivery will address these issues, delivering optimal drug concentrations with reduced toxicity. This investigation is germane;cumulative estimates regarding the incidence of voice disorders across the lifespan are not known, but are hypothesized to be higher than the 3-9% of the population figure that is often cited. This innovative approach has potential to evolve to the clinic across multiple organ systems.

Public Health Relevance

Vocal fold fibrosis is a source of common, debilitating voice disorders and treatments remain unsatisfactory. We seek to employ RNA-based therapeutics and furthermore optimize in vivo delivery of these compounds with the ultimate goal of facilitating a more regenerative model of healing in the vocal folds.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
1R01DC013277-01A1
Application #
8762049
Study Section
Motor Function, Speech and Rehabilitation Study Section (MFSR)
Program Officer
Shekim, Lana O
Project Start
2014-06-19
Project End
2019-05-31
Budget Start
2014-06-19
Budget End
2015-05-31
Support Year
1
Fiscal Year
2014
Total Cost
$420,968
Indirect Cost
$171,336
Name
New York University
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10016