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Pharmaceuticals
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Drug Candidates for Allergic Diseases
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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 (25 April 2025) | Viewed by 39292

Special Issue Editor

Prof. Dr. Luis Manuel Teran

E-Mail Website
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 (9 papers)

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Research

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13 pages, 6405 KiB  
Article
Adjuvant Effect of Lactobacillus paracasei in Sublingual Immunotherapy of Asthmatic Mice
by Dhafer Alwayli, Xiaoli Jiang, Jiaxu Liang, Syed Rafiq Hussain Shah, Atta Ullah, Mohammed F. Z. Abusidu and Wen Shu
Pharmaceuticals 2024, 17(12), 1580; https://doi.org/10.3390/ph17121580 - 24 Nov 2024
Viewed by 1504
Abstract
Background: Sublingual immunotherapy (SLIT) has shown promise in mitigating allergic asthma symptoms; nevertheless, its high dose and prolonged duration of treatment raise safety concerns. This study explored the potential of Lactobacillus paracasei (L. paracasei) to enhance the effectiveness of SLIT [...] Read more.
Background: Sublingual immunotherapy (SLIT) has shown promise in mitigating allergic asthma symptoms; nevertheless, its high dose and prolonged duration of treatment raise safety concerns. This study explored the potential of Lactobacillus paracasei (L. paracasei) to enhance the effectiveness of SLIT in a mouse model of allergic asthma. Methods: Allergic asthma was induced in Balb/c mice following sensitization and challenge with a house dust mite (HDM) allergen. Subsequently, the mice were subjected to SLIT (66 and 132 µg) either alone or in combination with L. paracasei supplementation. Asthma-associated parameters, including rubbing frequency, IgE level, cytokine profiles, and histological changes, were evaluated to assess treatment efficacy. Results: mice that received SLIT 132 µg combined with the probiotic (combined 132) demonstrated a significant reduction in allergic symptoms (rubbing). This treatment strategy led to a marked IgE and eosinophil level decrease in serum; an increase in anti-inflammatory cytokines like IFN-γ and IL-10; and a reduction in pro-inflammatory cytokines IL-17 and TNF-α. The combination therapy also mitigated lung inflammation and supported the restoration of the structural integrity of the colon, promoting the recovery of goblet cells and mucus secretion. Probiotic treatment alone also effectively reduced IgE levels, increased IFN-γ, and decreased levels of IL-17 and TNF-α. Conclusions: The adjuvant effect of L. paracasei in enhancing SLIT represents a promising approach for improving asthma treatment efficacy. Full article
(This article belongs to the Special Issue Drug Candidates for Allergic Diseases)
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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
Cited by 1 | Viewed by 1148
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 10 | Viewed by 5206
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 9 | Viewed by 3085
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, 720 KiB  
Review
Novel Approaches to Allergen Immunotherapy for Respiratory Allergies
by Mongkol Lao-Araya
Pharmaceuticals 2024, 17(11), 1510; https://doi.org/10.3390/ph17111510 - 9 Nov 2024
Cited by 1 | Viewed by 3288
Abstract
Allergen immunotherapy (AIT) remains the cornerstone for managing respiratory allergies, offering long-term symptom relief, disease modification, and prevention of disease progression. While novel approaches like intralymphatic and epicutaneous immunotherapy and the combination of allergens with adjuvants show promise, traditional methods remain effective and [...] Read more.
Allergen immunotherapy (AIT) remains the cornerstone for managing respiratory allergies, offering long-term symptom relief, disease modification, and prevention of disease progression. While novel approaches like intralymphatic and epicutaneous immunotherapy and the combination of allergens with adjuvants show promise, traditional methods remain effective and safe. Hypoallergenic T-cell peptide vaccines and recombinant allergens require further research to confirm their clinical benefits. Passive immunotherapy, while demonstrating effectiveness in specific cases, needs exploration of its long-term efficacy and broader applicability. Combining AIT with biologics may enhance safety and treatment outcomes. Despite emerging innovations, allergen-specific immunotherapy with natural allergen extracts remains the primary disease-modifying treatment, offering long-term symptom relief and prevention of disease progression. Continued research is essential to refine and optimize allergen immunotherapy strategies, providing patients with more effective and personalized treatment options. Full article
(This article belongs to the Special Issue Drug Candidates for Allergic Diseases)
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26 pages, 795 KiB  
Review
Therapies for Chronic Spontaneous Urticaria: Present and Future Developments
by Riccardo Asero, Paolo Calzari, Silvia Vaienti and Massimo Cugno
Pharmaceuticals 2024, 17(11), 1499; https://doi.org/10.3390/ph17111499 - 7 Nov 2024
Cited by 7 | Viewed by 11924
Abstract
Chronic spontaneous urticaria (CSU) is a complex dermatological condition characterized by recurrent wheals and/or angioedema lasting for more than six weeks, significantly impairing patients’ quality of life. According to European guidelines, the first step in treatment involves second-generation H1-antihistamines (sgAHs), which block peripheral [...] Read more.
Chronic spontaneous urticaria (CSU) is a complex dermatological condition characterized by recurrent wheals and/or angioedema lasting for more than six weeks, significantly impairing patients’ quality of life. According to European guidelines, the first step in treatment involves second-generation H1-antihistamines (sgAHs), which block peripheral H1 receptors to alleviate symptoms. In cases with inadequate responses, the dose of antihistamines can be increased by up to fourfold. If symptoms persist despite this adjustment, the next step involves the use of omalizumab, a monoclonal anti-IgE antibody, which has shown efficacy in the majority of cases. However, a subset of patients remains refractory, necessitating alternative treatments such as immunosuppressive agents like cyclosporine or azathioprine. To address these unmet needs, several new therapeutic targets are being explored. Among them, significant attention is being given to drugs that block Bruton’s tyrosine kinase (BTK), such as remibrutinib, which reduces mast cell activation. Therapies like dupilumab, which target the interleukin-4 (IL-4) and IL-13 pathways, are also under investigation. Additionally, molecules targeting the Mas-related G protein-coupled receptor X2 (MRGPRX2), and those inhibiting the tyrosine kinase receptor Kit, such as barzolvolimab, show promise in clinical studies. These emerging treatments offer new options for patients with difficult-to-treat CSU and have the potential to modify the natural course of the disease by targeting key immune pathways, helping to achieve longer-term remission. Further research is essential to better elucidate the pathophysiology of CSU and optimize treatment protocols to achieve long-term benefits in managing this condition. Altogether, the future of CSU treatments that target pathogenetic mechanisms seems promising. Full article
(This article belongs to the Special Issue Drug Candidates for Allergic Diseases)
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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 22 | Viewed by 8181
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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8 pages, 797 KiB  
Brief Report
Biologic Agents in Idiopathic Hypereosinophilic Syndrome
by Ourania Papaioannou, Fotios Sampsonas, Panagiota Tsiri, Vasilina Sotiropoulou, Ioannis Christopoulos, Dimitrios Komninos and Argyrios Tzouvelekis
Pharmaceuticals 2025, 18(4), 543; https://doi.org/10.3390/ph18040543 - 8 Apr 2025
Viewed by 761
Abstract
Background: Hypereosinophilic syndrome (HES) is a heterogeneous group of rare disorders defined by the presence of marked eosinophilia resulting in end organ damage. The diagnostic approach is multidisciplinary and treatment goals include reductions in flares and eosinophils with minimal drug-related side effects. Results: [...] Read more.
Background: Hypereosinophilic syndrome (HES) is a heterogeneous group of rare disorders defined by the presence of marked eosinophilia resulting in end organ damage. The diagnostic approach is multidisciplinary and treatment goals include reductions in flares and eosinophils with minimal drug-related side effects. Results: Eleven patients (n = 11) with a diagnosis of idiopathic HES were included in the study [M/F: 6/5, median age: 54 (95% CI: 38.2 to 68.5), smokers/never smokers: 5/6]. Asthma was present in the majority of them (n = 8, 72.7%); four patients (n = 4, 36.4%) presented with eosinophilic pleural effusions, two patients (n = 2, 18.2%) with cardiac arrhythmias, and one with bilateral eyelid angioedema. Eight patients (72.7%) were treated with mepolizumab (300 mg/month) and three (27.3%) with benralizumab (30 mg/4 weeks). The median values of eosinophils at baseline and 12 months after initiation of biologic agent were 3000 (95% CI: 2172 to 11,365) K/μL and 50 (95% CI: 3 to 190) K/μL, respectively, p = 0.0002. All patients with concomitant asthma (n = 8) experienced elimination of asthma flares, asthma control (ACQ < 0.75), functional improvement (mean ΔFEV1: 857 ± 594 mL), and an 82% reduction in oral corticosteroids, p = 0.0001. Materials and Methods: Patients with highly characterized idiopathic HES treated with anti-eosinophilic agents between 1 October 2019 and 1 October 2023 were retrospectively included in the study. The aim of this study was to present clinical, laboratory, and functional features and outcomes in patients with thoroughly investigated idiopathic HES treated with biologic agents targeting eosinophils. Conclusions: Biologic agents in patients with idiopathic HES—following thorough diagnostic investigation—are both safe and effective, sparing the toxicity of immunosuppressive agents. Real-life data from larger registries are greatly anticipated. Full article
(This article belongs to the Special Issue Drug Candidates for Allergic Diseases)
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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 6 | Viewed by 2638
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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