Combination Therapy for Suppressing IgE-Mediated Anaphylaxis
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Solution Overview
Problem
Current immunotherapeutic desensitization methods for allergic disorders, particularly those involving anti-IgE and anti-FcεRIα monoclonal antibodies, can induce IgE-mediated anaphylaxis, and existing treatments are limited in effectiveness for individuals allergic to multiple antigens or have serum antibodies that neutralize initial allergen doses, potentially leading to severe reactions.
Innovation Solution
Administering a combination of therapeutic agents including antihistamines, beta-adrenergic agonists, and tyrosine kinase antagonists, such as triprolidine, doxepin, indacaterol, terbutaline, albuterol, imatinib, and fostamatinib, to suppress IgE-mediated anaphylaxis, either alone or in combination with antibodies like anti-IgE or anti-FcεRIα monoclonal antibodies, as a pretreatment or concurrent therapy during desensitization processes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immunotherapeutic desensitization methods using anti-IgE or anti-FcεRIα monoclonal antibodies are administered, then allergic symptoms are treated, but IgE-mediated anaphylaxis is induced
Solution Approach 1:
The patent applies preliminary anti-action by administering blocking antibodies (anti-IgE or anti-FcεRIα) before allergen exposure to prevent IgE-mediated anaphylaxis. These blocking antibodies bind to IgE or FcεRIα in advance, preventing the formation of IgE-allergen complexes on mast cells and basophils, thereby suppressing the anaphylactic response while maintaining treatment effectiveness
Solution Approach 2:
The patent uses blocking antibodies as intermediary molecules that mediate between the allergen and the immune system. These antibodies serve as a protective barrier, intercepting IgE or FcεRIα before they can bind to allergens, thus preventing the harmful cascade while allowing controlled desensitization to proceed
2Productivity
If initial small allergen doses are administered during desensitization, then desensitization is attempted, but serum antibodies neutralize the allergen before it can access mast cell or basophil bound IgE, potentially leading to severe reactions
Solution Approach 1:
The patent applies preliminary action by administering blocking antibodies before allergen dosing to pre-establish protection against anaphylaxis. This preliminary intervention ensures that when allergen doses are administered during desensitization, the blocking antibodies are already in place to prevent neutralization failures and severe reactions, thereby improving both safety and desensitization efficiency
3Adaptability or versatility
If increasing doses of allergen are administered to induce desensitization, then tolerance is achieved, but the risk of severe anaphylactic reactions increases
Solution Approach 1:
The patent applies preliminary anti-action by administering blocking antibodies before escalating allergen doses during desensitization. This pre-protection allows the allergen doses to be increased to achieve desensitization tolerance while the blocking antibodies simultaneously prevent severe anaphylactic reactions, thereby enabling effective desensitization with improved safety
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The combination of these therapeutic agents effectively suppresses IgE-mediated anaphylaxis by inhibiting the release of vasoactive mediators and reducing symptoms, as demonstrated by temperature changes and mast cell degranulation measurements in animal models, providing a safer and more effective approach to desensitization.
Implementation Method 1
administering a combination of therapeutic agents selected from the group consisting of an antihistamine, one or more beta-adrenergic agonists, and one or more tyrosine kinase antagonists
Implementation Method 2
administering a combination of therapeutic agents selected from the group consisting of an antihistamine, one or more beta-adrenergic agonists, and one or more tyrosine kinase antagonists
Implementation Method 3
administering a combination of therapeutic agents selected from the group consisting of an antihistamine, one or more beta-adrenergic agonists, and one or more tyrosine kinase antagonists
Implementation Method 4
IgE primes the IgE-mediated allergic response by binding to Fc receptors found on the surface of mast cells and basophils. IgE that can specifically recognize an allergen has a unique, long-lived interaction with its high-affinity receptor FcεRI
Implementation Method 5
Immediate hypersensitivity reactions are the critical pathogenic mechanism in anaphylaxis and IgE-mediated food allergy. In both humans and mice, immediate hypersensitivity reactions can be mediated by antigen crosslinking of antigen-specific IgE bound to the high affinity IgE receptor, FcεRI, on mast cells and basophils
Data Source
AI summary
Methods for suppressing IgE-mediated anaphylaxis are provided herein, which include administering to a person in need thereof a combination of at least two therapeutic agents selected from the group consisting of an antihistamine, one or more beta-adrenergic agonists, and one or more tyrosine kinase antagonists. Also provided herein are methods of suppressing IgE-mediated anaphylaxis associated with immunotherapeutic desensitization of a subject, and pharmaceutical compositions for suppressing IgE-mediated anaphylaxis.