scholarly journals Targeting the FcεRI Pathway as a Potential Strategy to Prevent Food-Induced Anaphylaxis

2020 ◽  
Vol 11 ◽  
Author(s):  
Melanie C. Dispenza ◽  
Bruce S. Bochner ◽  
Donald W. MacGlashan

Despite attempts to halt it, the prevalence of food allergy is increasing, and there is an unmet need for strategies to prevent morbidity and mortality from food-induced allergic reactions. There are no known medications that can prevent anaphylaxis, but several novel therapies show promise for the prevention of food-induced anaphylaxis through targeting of the high-affinity IgE receptor (FcϵRI) pathway. This pathway includes multiple candidate targets, including tyrosine kinases and the receptor itself. Small molecule inhibitors of essential kinases have rapid onset of action and transient efficacy, which may be beneficial for short-term use for immunotherapy buildup or desensitizations. Short courses of FDA-approved inhibitors of Bruton’s tyrosine kinase can eliminate IgE-mediated basophil activation and reduce food skin test size in allergic adults, and prevent IgE-mediated anaphylaxis in humanized mice. In contrast, biologics may provide longer-lasting protection, albeit with slower onset. Omalizumab is an anti-IgE antibody that sequesters IgE, thereby reducing FcϵRI expression on mast cells and basophils. As a monotherapy, it can increase the clinical threshold dose of food allergen, and when used as an adjunct for food immunotherapy, it decreases severe reactions during buildup phase. Finally, lirentelimab, an anti-Siglec-8 antibody currently in clinical trials, can prevent IgE-mediated anaphylaxis in mice through mast cell inhibition. This review discusses these and other emerging therapies as potential strategies for preventing food-induced anaphylaxis. In contrast to other food allergy treatments which largely focus on individual allergens, blockade of the FcϵRI pathway has the advantage of preventing clinical reactivity from any food.

Alergologia ◽  
2019 ◽  
Vol 4 (3) ◽  
pp. 154
Author(s):  
G.M. Feketea ◽  
Corina Bocșan
Keyword(s):  

2020 ◽  
pp. 7-24
Author(s):  
Zhanna Kozlova ◽  
Ivan Krasnyuk ◽  
Yuliya Lebedeva ◽  
Ekaterina Odintsova

Oral mucosal drug delivery is an alternative method of systemic delivery with several advantages over both injectable and enteral methods. Drugs that are absorbed through the oral mucosa directly enter the systemic circulation, passing through the gastrointestinal tract and first-pass metabolism in the liver due to oral mucosa being highly vascularised. This results in rapid onset of action for some drugs because of a more comfortable and convenient way of delivery than the intravenous one. But not all drugs can be administered through the oral mucosa due to characteristics of the oral mucosa and physical and chemical properties of the drug.


2020 ◽  
Vol 5 (3) ◽  
pp. 4-11
Author(s):  
E. V. Kryuchenko ◽  
Yu. A. Kuzlyakina ◽  
V. S. Zamula ◽  
I. M. Chernukha

The article discusses the definition and mechanism of IgE‑mediated food allergy, provides an overview of the legal regulation of the production and labeling of allergen-containing food products. In order to prevent the inadvertent appearance of allergens in products during their production, an allergenomics procedure is required — a comprehensive assessment of the allergic potential of a food product: allergenicity of product ingredients, risk analysis, and the procedure for managing allergens in the production.


2019 ◽  
Vol 13 (2) ◽  
pp. 83-90 ◽  
Author(s):  
Hetal Patel ◽  
Mukesh Gohel

Enteric coated dosage form bypasses the stomach and releases the drug into the small intestine. Advantages of enteric coated pellets in comparison with enteric coated tablets are a) Pellets provide rapid onset of action and faster drug release due to the smaller size than tablets and b) Pellets exhibit less residence time of acid-labile drugs in the stomach compared to tablets. Dosage form coat can be damaged by longer resistance time in the stomach. The present review summarizes the current state of enteric coated pellets where core pellets are prepared by extrusion-spheronization technique and the enteric coating is applied in a fluidized bed processor. Two approaches are involved in the preparation of core pellets. In the first approach, a mixture of drug and excipient(s)/co-processed excipient is passed through extruders to prepare core pellets. In the second approach, excipient core pellets are prepared by extrusion technique and the drug is layered onto it before the enteric coating. The excipients present in the core pellets decide immediate or extended release of drug in the intestine. The coprocessed excipient pellets provide less batch variability and provide a platform for layering of many drugs before enteric coating. Some patents included enteric coating pellets [CN105456223 (A), CN105596310 (A), CN105616371 (A), CN105663095 (A), CN101611766B, CN106511862 (A), CN106668018 (A), CN106727381 (A), CN106924222 (A), TW200624127 (A), US 2017/0165248A1, US 2017/0224720A1] are discussed.


2021 ◽  
Vol 10 (11) ◽  
pp. 2468
Author(s):  
Vincent Martin ◽  
John Hoekman ◽  
Sheena K. Aurora ◽  
Stephen B. Shrewsbury

The acute treatment of migraine requires effective drugs that are well tolerated and provide rapid and consistent pain relief. Oral tablets are the most commonly used acute treatment for migraine; however, their effectiveness is limited by the rate of gastrointestinal (GI) tract absorption and first-pass hepatic metabolism, and they may not be ideal for patients experiencing GI motility issues. Nasal delivery is an attractive alternative route as it may circumvent GI tract absorption, avoid first-pass metabolism in the liver, and potentially reduce the frequency of GI adverse events. The large surface area and high vascularity within the nose may permit rapid absorption of therapeutics into the systemic circulation, allowing for rapid onset of action. However, the site of drug deposition (upper versus lower nasal cavity) may influence drug pharmacokinetics. Most approved nasal migraine therapies target the lower nasal space where the epithelium is less permeable, and they may be quickly cleared away due to increased ciliary function or dripping from the nose or swallowing, resulting in variable absorption and limited bioavailability. Together with its abundant vascularization, relative mucosal thickness stability, and low clearance rates, the upper nasal space harnesses the benefits of nasal delivery to potentially maximize drug efficacy.


2011 ◽  
Vol 32 (6) ◽  
pp. 47-55 ◽  
Author(s):  
S. Tolga Yavuz ◽  
Umit M. Sahiner ◽  
Betul Buyuktiryaki ◽  
Ozge U. Soyer ◽  
Ayfer Tuncer ◽  
...  

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