(717) Optimization Of A Biomolecule-Based Therapy In Vivo Study For Treatment Of Vocal Fold Paralysis

Introduction: Our lab has developed a novel biotherapeutic cocktail of three injectable molecules: Agrin, Acetylcholine (Ach), and Neuregulin (NRG) aimed at treating vocal fold paralysis (VFP) by medializing the immobile vocal fold while promoting neuronal regeneration. This research aims to determine the optimal concentration of each ingredient within the biomolecular cocktail.

Methods: C57BL/6 mice underwent RLN transection and thyroarytenoid injection with one of the four different treatment cocktail concentrations or a saline control. The groups had the same concentration of Ach and consisted of various concentrations of Agrin and NRG. Assessment of glottic function was determined 28 days following RLN transection and vocal fold injection via laryngeal electromyography (L-EMG) and video laryngoscopy. Histopathology analysis with immunohistochemistry (IHC) and qPCR was utilized to assess reinnervation changes within the harvested larynges.

Results: Preliminary results show increased reinnervation of the adductor complex with all of the biomolecular treatments resulting in significantly increased L-EMG area under the curve (AUC) (p < 0.05) compared with control. The treatment group with high Agrin/high NRG concentrations performed the best (Mean AUC; High dose Agrin/NRG= 0.99, Control=0.23). Preliminary IHC analysis aligns with functional videolaryngoscopy and stimulated L-EMG data.

Conclusions: The novel biomolecular cocktail has promising results showing significantly increased EMG data of the thyroarytenoid muscle in all concentration groups compared to the saline control. High dose NRG/ high dose Agrin treatment showed the most significant increase compared to controls, suggesting a potentially synergistic, dose-dependent effect.