MRGPRD Agonists for Mast Cell Degranulation Suppression
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing treatments for conditions associated with mast cell activation, such as urticaria, mastocytosis, and food allergy, are inadequate in effectively suppressing inflammation and mast cell degranulation.
Innovation Solution
Administration of MRGPRD agonists, including beta alanine, gamma-aminobutyric acid, and beta aminoisobutyric acid, or their pharmaceutically-acceptable salts, to down-regulate mast cell degranulation and inflammation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If mast-cell stabilizers or antihistamines are used to inhibit mast cell mediator release, then allergic reactions are attenuated, but the treatments are inadequate for effectively suppressing inflammation and mast cell degranulation in conditions like urticaria and mastocytosis
Solution Approach 1:
The patent changes the pharmacological parameter from histamine receptor blockade (antihistamines) or membrane stabilization (mast-cell stabilizers) to GPCR activation (MRGPRD agonism). This parameter change enables more effective suppression of mast cell degranulation and inflammation across multiple conditions including urticaria, mastocytosis, and allergic reactions, overcoming the limitations of existing treatments
2Object-affected harmful factors
If existing medications are administered to suppress mast cell activation, then some inflammatory symptoms are reduced, but the treatments fail to provide adequate suppression of inflammation and mast cell degranulation
Solution Approach 1:
The patent introduces MRGPRD agonists as intermediary substances that mediate the suppression of mast cell degranulation. These agonists activate MRGPRD receptors on mast cells, triggering a signaling cascade that ultimately inhibits degranulation and inflammation, providing a more reliable therapeutic mechanism than existing medications
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 MRGPRD agonists effectively reduce mast cell activation, inflammation, and enhance wound healing, providing therapeutic benefits for conditions like urticaria, mastocytosis, and food allergy.
Implementation Method 1
Mast cells also express surface Mas-related G protein receptors. These receptors bind to specific ligands including the neuropeptide Substance P, the antimicrobial peptide LL37 as well as exogenous agents such as certain drugs and components of house dust mites. Engagement of this receptor results in release of several biologically active molecules including cytokines and proteases
Data Source
AI summary
Provided herein are methods of treating conditions associated with activation or over-activation of mast cells is acute or chronic urticaria, mastocytosis or any subtype of mastocytosis, pseudo-allergy, any form of dermatitis, such as contact or atopic dermatitis, wound healing, rosacea, acne, or psoriasis, food allergy, or irritable bowel syndrome. The method comprises administering a MRGPRD agonist, such as beta alanine, GABA, β-AIBA, or 5-oxoETE to a patient to treat the condition. Topical, enteric, delayed-release, or aerosol dosage forms comprising beta-alanine also are provided.