Intranasal administration of a synthetic TLR4 agonist INI-2004 significantly reduces allergy symptoms following therapeutic administration in a murine model of allergic sensitization.
Front Immunol
; 15: 1421758, 2024.
Article
em En
| MEDLINE
| ID: mdl-39108263
ABSTRACT
Introduction:
Atopic diseases have been steadily increasing over the past decades and effective disease-modifying treatment options are urgently needed. These studies introduce a novel synthetic Toll-like receptor 4 (TLR4) agonist, INI-2004, with remarkable efficacy as a therapeutic intranasal treatment for seasonal allergic rhinitis.Methods:
Using a murine airway allergic sensitization model, the impact of INI-2004 on allergic responses was assessed.Results:
One or two intranasal doses of INI-2004 significantly reduced airway resistance, eosinophil influx, and Th2 cytokine production - providing strong evidence of allergic desensitization. Further investigations revealed that a liposomal formulation of INI-2004 exhibited better safety and efficacy profiles compared to aqueous formulations. Importantly, the liposomal formulation demonstrated a 1000-fold increase in the maximum tolerated intravenous dose in pigs. Pre-clinical GLP toxicology studies in rats and pigs confirmed the safety of liposomal INI-2004, supporting its selection for human clinical trials.Discussion:
These findings lay the groundwork for the ongoing clinical evaluation of INI-2004 in allergic rhinitis as a stand-alone therapy for individuals poly-sensitized to multiple seasonal allergens. The study underscores the significance of innovative immunotherapy approaches in reshaping the landscape of allergic rhinitis management.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Administração Intranasal
/
Modelos Animais de Doenças
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Receptor 4 Toll-Like
Limite:
Animals
Idioma:
En
Revista:
Front Immunol
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos