A novel botulinum neurotoxin topical gel: treatment of allergic rhinitis in rats and comparative safety profile

Background: Rhinitis affects a significant proportion of adults and children with typically seasonal or chronic symptoms. Botulinum neurotoxin type A (BoNTA) is a well-known cholinergic antagonist widely used in a number of approved neurological and esthetic indications. This study was designed to assess the therapeutic effect of RT001, a novel topical gel formulation of BoNTA, in the treatment of allergic rhinitis using a rat model and to compare its safety profile with that of an aqueous formulation of BoNTA complex.

Methods: A rat model of allergic rhinitis was used involving induction of classic rhinitis signs (sneezing and nasal itch) in addition to nasal inflammatory pathology to assess the degree of therapeutic effect of RT001. Comparative safety of RT001 and BoNTA complex was assessed in guinea pigs based on lethality and body weight gain.

Results: Clinical signs of rhinitis were significantly (p <0.01) relieved after a single intranasal administration of RT001 and resolved to normal baseline levels within 5 days after treatment. Mucosal inflammation characterized by edema, congestion, and vascular dilatation along with increased expression of vasoactive intestinal peptide was noted in control animals after allergy induction, whereas RT001 treatment resolved inflammation to essentially normal baseline levels. Safety studies in guinea pigs via intranasal dosing revealed similar to 31-fold greater safety factor for RT001 when compared with BoNTA complex.

Conclusion: These results suggest that topical intranasal application of RT001 is effective in relief of clinical signs and inflammatory pathology associated with allergic rhinitis in a rodent model and may provide a safe treatment for rhinitis.