Drug Candidates for Allergic Diseases

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: closed (20 September 2024) | Viewed by 14963

Special Issue Editor


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Guest Editor
Department of Immunogenetics and Allergy, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico
Interests: allergy; proteomics; asthma

Special Issue Information

Dear Colleagues,

Over the last two decades, novel drugs have emerged, paving the way for the personalized management of allergic diseases. Bronchoscopy studies and mouse models of asthma have provided initial insights into the mechanisms of allergic inflammation establishing, the role of Th2 type 2 cytokines including IL-4 and IL-5 IL-13 that led to the development of several monoclonal antibodies (mAbs) targeting these cytokines. Omalizumab was the first mAb used successfully to treat severe asthma patients. Subsequently, other drugs emerged, including antibodies that block IL-5 (mepolizumab, reslizumab) and the IL-5 receptor (benralizumab), the IL-4/IL-13 receptor alpha chain (dupilumab), and the thymic stromal lymphopoietin (Tezepelumab). These novel biologicals have been shown to be good alternative therapies to corticosteroids, particularly in severe asthma management, where they have improved the quality of life of many patients. Given the success in asthma, these drugs have been used in other allergic diseases, including chronic rhinosinusitis with nasal polyps (CRSwNP), atopic dermatitis, eosinophilic esophagitis, and chronic urticaria. Currently, a number of novel antagonists targeting other inflammatory mediators are still in preclinical stages.

This Special Edition will assemble a series of articles that examine the effects of novel drugs in allergic diseases.

Prof. Dr. Luis Manuel Teran
Guest Editor

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Keywords

  • allergic disease
  • asthma
  • CRSwNP
  • atopic dermatitis
  • biologicals
  • chronic urticaria
  • pharmacology
  • novel drugs

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Published Papers (5 papers)

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Research

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13 pages, 5964 KiB  
Article
β-Tocotrienol Decreases PDGF-BB-Induced Proliferation and Migration of Human Airway Smooth Muscle Cells by Inhibiting RhoA and Reducing ROS Production
by Aditya Sri Listyoko, Ryota Okazaki, Tomoya Harada, Miki Takata, Masato Morita, Hiroki Ishikawa, Yoshihiro Funaki and Akira Yamasaki
Pharmaceuticals 2024, 17(6), 712; https://doi.org/10.3390/ph17060712 - 30 May 2024
Viewed by 656
Abstract
Background: Tocotrienols exhibit antioxidant and anti-inflammatory activities. RhoA, a small GTPase protein, plays a crucial role in regulating contractility in airway smooth muscle (ASM). Previous studies have demonstrated that γ-tocotrienols reduce ASM proliferation and migration by inhibiting the activation of RhoA. In this [...] Read more.
Background: Tocotrienols exhibit antioxidant and anti-inflammatory activities. RhoA, a small GTPase protein, plays a crucial role in regulating contractility in airway smooth muscle (ASM). Previous studies have demonstrated that γ-tocotrienols reduce ASM proliferation and migration by inhibiting the activation of RhoA. In this present study, we investigate the effect of another vitamin E isoform, β-tocotrienols, on human ASM cell proliferation and migration stimulated by platelet-derived growth factor-BB (PDGF-BB). Methods: Human ASM cells were pre-treated with β-tocotrienol prior to being stimulated with PDGF-BB to induce ASM cell proliferation and migration. The proliferation and migration of PDGF-BB-induced human ASM cells were assessed using colorimetric and transwell migration assays. The intracellular ROS assay kit was employed to quantify reactive oxygen species (ROS) in human ASM cells. Additionally, we explored the effect of β-tocotrienols on the signaling pathways involved in PDGF-BB-induced ASM proliferation and migration. Results: β-tocotrienol inhibited PDGF-BB-induced ASM cell proliferation and migration by reducing RhoA activation and ROS production. However, in this present study, β-tocotrienol did not affect the signaling pathways associated with cyclin D1, phosphorylated Akt1, and ERK1/2. Conclusions: In conclusion, the inhibition of RhoA activation and ROS production by β-tocotrienol, resulting in the reduction in human ASM proliferation and migration, suggests its potential as a treatment for asthma airway remodeling. Full article
(This article belongs to the Special Issue Drug Candidates for Allergic Diseases)
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11 pages, 1406 KiB  
Article
Sustained Effectiveness of Upadacitinib in Moderate-to-Severe Atopic Dermatitis: A 48-Week Real-World Study
by Teppei Hagino, Risa Hamada, Mai Yoshida, Hidehisa Saeki, Eita Fujimoto and Naoko Kanda
Pharmaceuticals 2024, 17(4), 519; https://doi.org/10.3390/ph17040519 - 18 Apr 2024
Cited by 4 | Viewed by 2946
Abstract
Clinical trials and real-world studies have shown the effectiveness of upadacitinib for treating rash and pruritus in patients with atopic dermatitis (AD). This study aimed to determine whether the early reduction in rash or pruritus at week 12 of upadacitinib treatment could be [...] Read more.
Clinical trials and real-world studies have shown the effectiveness of upadacitinib for treating rash and pruritus in patients with atopic dermatitis (AD). This study aimed to determine whether the early reduction in rash or pruritus at week 12 of upadacitinib treatment could be maintained at later treatment stages. This retrospective study involved 227 and 73 patients with moderate-to-severe AD treated with 15 and 30 mg upadacitinib daily, respectively. The eczema area and severity index (EASI) scores, peak pruritus numerical rating scale (PP-NRS), and investigator’s global assessment (IGA) were analyzed. At week 12, patients were divided into achievers and non-achievers of EASI 75, 90, 100, absolute EASI ≤ 2, IGA0/1, PP-NRS4, or absolute PP-NRS ≤ 1. Achievement rates for each endpoint were assessed at later time points (weeks 24, 36, and 48) in both groups. Week 12 achievers largely maintained their endpoint achievements until week 48, regardless of dosage (15 mg or 30 mg). Week 12 non-achievers saw an increasing achievement rate of EASI 75 until week 48. The initial reduction in rash and pruritus at week 12 persisted until week 48 with upadacitinib treatment, suggesting potential benefits for patients requiring prolonged treatment despite not achieving EASI 75 at week 12. Full article
(This article belongs to the Special Issue Drug Candidates for Allergic Diseases)
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19 pages, 3411 KiB  
Article
Development of an Oral Isoliquiritigenin Self-Nano-Emulsifying Drug Delivery System (ILQ-SNEDDS) for Effective Treatment of Eosinophilic Esophagitis Induced by Food Allergy
by Mingzhuo Cao, Yuan Wang, Heyun Jing, Zeqian Wang, Yijia Meng, Yu Geng, Mingsan Miao and Xiu-Min Li
Pharmaceuticals 2022, 15(12), 1587; https://doi.org/10.3390/ph15121587 - 19 Dec 2022
Cited by 5 | Viewed by 2439
Abstract
Isoliquiritigenin (ILQ) is a natural flavonoid with various pharmacological activities. In this study, we optimized the preparation method of self-nano-emulsion-loaded ILQ to further improve its bioavailability based on our previous study. In addition, its effect on the treatment of eosinophilic esophagitis was also [...] Read more.
Isoliquiritigenin (ILQ) is a natural flavonoid with various pharmacological activities. In this study, we optimized the preparation method of self-nano-emulsion-loaded ILQ to further improve its bioavailability based on our previous study. In addition, its effect on the treatment of eosinophilic esophagitis was also evaluated. Combined surfactants and co-surfactants were screened, and the optimal formulation of ILQ-SNEDDS was determined according to droplet size, droplet dispersity index (DDI), and drug loading. The formulation was composed of ethyl oleate (oil phase), Tween 80 & Cremophor EL (surfactant, 7:3), and PEG 400 & 1,2-propylene glycol (cosurfactant, 1:1), with a mass ratio of 3:6:1. Its physicochemical properties, including drug loading, droplets’ size, Zeta potential, appearance, and Fourier transform infrared (FTIR) spectroscopy, were characterized. In vitro release profile, in situ intestinal absorption, and in vivo pharmacokinetics were applied to confirm the improvement of oral ILQ bioavailability by NEDDS. Finally, the efficacy of ILQ-SNEDDS in the treatment of food allergy-induced eosinophilic esophagitis (EOE) was further evaluated. When the ILQ drug loading was 77.9 mg/g, ILQ-SNEDDS could self-assemble into sub-spherical uniform droplets with an average size of about 33.4 ± 2.46 nm (PDI about 0.10 ± 0.05) and a Zeta potential of approximately −10.05 ± 3.23 mV. In situ intestinal absorption showed that optimized SNEDDS significantly increased the apparent permeability coefficient of ILQ by 1.69 times, and the pharmacokinetic parameters also confirmed that SNEDDS sharply increased the max plasma concentration and bioavailability of ILQ by 3.47 and 2.02 times, respectively. ILQ-SNEDDS also significantly improved the apparent signs, allergic index, hypothermia and body weight of EoE model mice. ILQ-SNEDDS treatment significantly reduced the levels of inflammatory cytokines, such as TNF-α, IL-4, and IL-5, and the level of PPE-s-IgE in serum, and significantly inhibited the expression of TGF-β1 in esophageal tissue. SNEDDS significantly improved the solubility and bioavailability of ILQ. Additionally, ILQ-SNEDDS treatment attenuated symptomatology of EoE model mice, which was associated with inhibiting the production of TH2 inflammatory cytokines and PPE-s-IgE and the expression of TGF-β1. The above results shows that ILQ-SNEDDS has great potential as a good candidate for the treatment of eosinophilic esophagitis. Full article
(This article belongs to the Special Issue Drug Candidates for Allergic Diseases)
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Review

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20 pages, 1915 KiB  
Review
Biologic Therapies for Asthma and Allergic Disease: Past, Present, and Future
by Fernando Ramírez-Jiménez, Gandhi Fernando Pavón-Romero, Juancarlos Manuel Velásquez-Rodríguez, Mariana Itzel López-Garza, José Fernando Lazarini-Ruiz, Katia Vanessa Gutiérrez-Quiroz and Luis M. Teran
Pharmaceuticals 2023, 16(2), 270; https://doi.org/10.3390/ph16020270 - 10 Feb 2023
Cited by 7 | Viewed by 5647
Abstract
The discovery of the mechanism underlying allergic disease, mouse models of asthma, and bronchoscopy studies provided initial insights into the role of Th2-type cytokines, including interlukin (IL)-4, IL-5 and IL-13, which became the target of monoclonal antibody therapy. Omalizumab, Benralizumab, Mepolizumab, Reslizumab, and [...] Read more.
The discovery of the mechanism underlying allergic disease, mouse models of asthma, and bronchoscopy studies provided initial insights into the role of Th2-type cytokines, including interlukin (IL)-4, IL-5 and IL-13, which became the target of monoclonal antibody therapy. Omalizumab, Benralizumab, Mepolizumab, Reslizumab, and Tezepelumab have been approved. These biologicals have been shown to be good alternative therapies to corticosteroids, particularly in severe asthma management, where they can improve the quality of life of many patients. Given the success in asthma, these drugs have been used in other diseases with type 2 inflammation, including chronic rhinosinusitis with nasal polyps (CRSwNP), atopic dermatitis, and chronic urticaria. Like the Th2-type cytokines, chemokines have also been the target of novel monoclonal therapies. However, they have not proved successful to date. In this review, targeted therapy is addressed from its inception to future applications in allergic diseases. Full article
(This article belongs to the Special Issue Drug Candidates for Allergic Diseases)
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Other

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15 pages, 1781 KiB  
Systematic Review
Evidence Gaps in Clinical Trials of Pharmacologic Treatment for H1-Antihistamine-Refractory Chronic Spontaneous Urticaria: A Systematic Review and Future Perspectives
by Surapon Nochaiwong, Mati Chuamanochan, Chidchanok Ruengorn and Kednapa Thavorn
Pharmaceuticals 2022, 15(10), 1246; https://doi.org/10.3390/ph15101246 - 10 Oct 2022
Cited by 5 | Viewed by 2131
Abstract
No data addressing issues concerning disparities in participant and trial characteristics and trial outcome reporting have been established in clinical trials for H1-antihistamine-refractory chronic spontaneous urticaria (CSU). To better harmonize and compare the different treatment interventions, we systematically evaluated the overall landscape of [...] Read more.
No data addressing issues concerning disparities in participant and trial characteristics and trial outcome reporting have been established in clinical trials for H1-antihistamine-refractory chronic spontaneous urticaria (CSU). To better harmonize and compare the different treatment interventions, we systematically evaluated the overall landscape of pharmacological treatments for H1-antihistamine-refractory CSU clinical trials published between 2000 and 2021. This systematic review included 23 randomized clinical trials involving 2480 participants from 22 countries. We found significant increases in the number of globally published and newly tested drugs, especially biologic drugs. Regarding relatively small trials, we found that people living with H1-antihistamine-refractory CSU who were identified as members of minority groups (non-white population), populations of regions other than North America/Europe, and populations of low- to lower/upper-middle-income countries are underrepresented. Most trials were designed to evaluate treatment efficacy and safety profiles; however, less than half of the included trials reported the patient’s perspective in terms of patient-reported outcomes. Disparities in outcome reporting, including clinimetric tools for assessing treatment response and outcome sets, were observed. To close the evidence gap in H1-antihistamine-refractory CSU trials, strategies for improving trial and participant enrollment and standardizing core outcome sets for trial reporting are needed. Full article
(This article belongs to the Special Issue Drug Candidates for Allergic Diseases)
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