Allergic diseases constitute the most common chronic diseases of childhood and cause significant morbidity. However, allergen-specific injection immunotherapy, which is not acceptable to many children and may be too risky for some types of allergy, remains the only approved disease modifying treatment for allergic diseases. Sublingual immunotherapy has been shown to be safer for treatment of both food and aeroallergies, but current methods are not optimized for efficacy, safety or practicality, and are not approved for use in the U.S.. A mucoadhesive, dissolving film improves upon current liquid methods of immunotherapy because it (1) prolongs contact between antigen presenting cells and allergen, which is vital for the efficacy of immunotherapy, (2) allows for more flexible dosing, with both higher and lower standardized doses than are currently available, (3) is a more practical method for use in children, requiring little cooperation and, (4) unlike liquids, is not subject to the risk of aspiration. We have developed such a film for use in the treatment of peanut allergy. In this grant, we propose to extend this method to other important allergens for children and explore methods to optimize its use in children.
Aim 1 is to develop and refine orally dissolving strips for treatment of cockroach and cat allergies. These allergies are two of the most important contributors to allergic rhinitis and asthma in children, and each present unique challenges and opportunities for design of a film.
Aim 2 is to optimize the pharmacokinetics and palatability of a dissolving film by evaluating the effect of different placements in the mouth and, if need be, formulations on persistence of allergen in the mouth and on palatability. This methods developed here have to the potential to address the fundamental problems that currently limit or entirely prevent translation of immunotherapy in children from research settings to the clinic.
This proposal is to develop a novel treatment for the most common chronic diseases affecting children. The method discussed addresses the fundamental problems that currently limit, or entirely prevent, translation of orally delivered immunotherapy in children from research settings to the clinic. Eventually, the methods developed here may have applications not only to allergy, but also to vaccination, where oral formulations could solve many fundamental problems, especially in developing countries.
|Gorelik, Mark; Narisety, Satya D; Guerrerio, Anthony L et al. (2015) Suppression of the immunologic response to peanut during immunotherapy is often transient. J Allergy Clin Immunol 135:1283-92|
|Narisety, Satya D; Frischmeyer-Guerrerio, Pamela A; Keet, Corinne A et al. (2015) A randomized, double-blind, placebo-controlled pilot study of sublingual versus oral immunotherapy for the treatment of peanut allergy. J Allergy Clin Immunol 135:1275-82.e1-6|
|Frischmeyer-Guerrerio, Pamela A; Keet, Corinne A; Guerrerio, Anthony L et al. (2014) Modulation of dendritic cell innate and adaptive immune functions by oral and sublingual immunotherapy. Clin Immunol 155:47-59|
|Keet, Corinne A; Wood, Robert A (2014) Emerging therapies for food allergy. J Clin Invest 124:1880-6|
|Schroeder, John T; Bieneman, Anja P; Chichester, Kristin L et al. (2013) Spontaneous basophil responses in food-allergic children are transferable by plasma and are IgE-dependent. J Allergy Clin Immunol 132:1428-31|