ABSTRACT
Many diseases originate from either the absence or defective expression of a given protein. For some of them, the lacking protein is secreted or can be taken up by cells when delivered exogenously. In such cases, therapies initially involved administering the physiological protein extracted from human tissues. Subsequently, genetic engineering enabled the production of proteins through cell fermentation after introducing the corresponding gene. For many other pathologies, the deficient protein cannot be delivered exogenously. Thus, an endogenous production of the therapeutic protein by the cells themselves is necessary. Messenger RNA (mRNA) technology, like its predecessor DNA, aims to supplement the genetic information needed to produce the therapeutic protein within the cells. However, unlike DNA-based therapies, mRNA transfer allows for transient expression of the protein of interest, which offers an advantage in numerous pathologies. Nonetheless, mastering the quantity, quality, and spatio-temporal regulation of protein production encoded by therapeutic mRNA remains a significant challenge for the development of this approach.
Title: « ReNAissance ¼1 des biothérapies par ARN. Abstract: Nombre de maladies ont pour origine une absence d'expression ou une expression défectueuse d'une protéine donnée. Pour certaines d'entre elles, la protéine faisant défaut est circulante et peut être captée par les cellules lorsqu'elle est délivrée de façon exogène. Dans ce cas, les thérapies ont d'abord consisté en l'administration de la protéine thérapeutique extraite de tissus humains. Par la suite, le génie génétique a permis la production des protéines par fermentation de cellules après y avoir introduit le gène correspondant. Pour beaucoup d'autres maladies, la protéine faisant défaut ne peut être délivrée de façon exogène. Une production endogène de la protéine thérapeutique, par les cellules elles-mêmes est donc nécessaire. La technologie de l'ARN messager (ARNm), comme celle la précédant de l'ADN, se propose de supplémenter, au cÅur des cellules, l'information génétique nécessaire pour produire elles-mêmes la protéine thérapeutique. Cependant, contrairement aux thérapies utilisant l'ADN, le transfert d'ARNm permet une expression transitoire de la protéine d'intérêt ce qui constitue un avantage dans nombre de maladies. La maîtrise de la quantité, de la qualité et de la régulation spatio-temporelle de la production d'une protéine codée par l'ARNm thérapeutique représente, néanmoins, un défi important pour le développement de cette approche.
Subject(s)
RNA, Messenger , Humans , RNA, Messenger/genetics , Genetic Therapy/methods , Genetic Therapy/trends , Animals , Biological Therapy/methods , Biological Therapy/trends , RNA/geneticsABSTRACT
INTRODUCTION: Chronic spontaneous urticaria (CSU) poses significant challenges, especially in pediatric and adolescent patients, impacting physical, emotional, and social well-being. Recent biologic breakthroughs offer promise, however, data on safety and efficacy in this population remain limited. AREAS COVERED: This review examines current biologic treatments in pediatrics and adolescents with CSU and explores the rapidly emerging landscape. EXPERT OPINION: Despite omalizumab's approval for allergic asthma in children since 2009, its delayed approval for CSU raises questions. Ligelizumab, a next-generation anti-IgE mAb, showed effectiveness in adults but lacks pediatric studies. CT-P39, a biosimilar to omalizumab, demonstrates promise, yet adolescent-specific outcomes are undisclosed. Dupilumab's recent approval for atopic dermatitis in children from 6 months onwards signifies progress. Expert opinion underscores the scarcity of controlled trials in pediatric and adolescent CSU, emphasizing the need for comprehensive studies. Age-specific data and collaboration are crucial for addressing research gaps and expanding indications for pediatric CSU treatment. The recently validated UAS7 parameter in children marks a milestone for prospective clinical trials. Despite challenges, the biology therapy outlook for pediatric and adolescent CSU is promising. Importantly, studies indicate that pediatric CSU is at least as prevalent as in adults, highlighting the need for approved treatments in this population.
Subject(s)
Chronic Urticaria , Humans , Adolescent , Child , Chronic Urticaria/drug therapy , Chronic Urticaria/immunology , Biological Therapy/trends , Biological Therapy/methods , Biological Products/therapeutic use , Biological Products/adverse effectsABSTRACT
Lectins or clusters of carbohydrate-binding proteins of non-immune origin are distributed chiefly in the Plantae. Lectins have potent anti-infectivity properties for several RNA viruses including SARS-CoV-2. The primary purpose of this review is to review the ability of lectins mediated potential biotherapeutic and bioprophylactic strategy against coronavirus causing COVID-19. Lectins have binding affinity to the glycans of SARS-COV-2 Spike glycoprotein that has N-glycosylation sites. Apart from this, the complement lectin pathway is a "first line host defense" against the viral infection that is activated by mannose-binding lectins. Mannose-binding lectins deficiency in serum influences innate immunity of the host and facilitates infectious diseases including COVID-19. Our accumulated evidence obtained from scientific databases particularly PubMed and Google Scholar databases indicate that mannose-specific/mannose-binding lectins (MBL) have potent efficacies like anti-infectivity, complement cascade induction, immunoadjuvants, DC-SIGN antagonists, or glycomimetic approach, which can prove useful in the strategy of COVID-19 combat along with the glycobiological aspects of SARS-CoV-2 infections and antiviral immunity. For example, plant-derived mannose-specific lectins BanLac, FRIL, Lentil, and GRFT from red algae can inhibit and neutralize SARS-CoV-2 infectivity, as confirmed with in-vitro, in-vivo, and in-silico assessments. Furthermore, Bangladesh has a noteworthy resource of antiviral medicinal plants as well as plant lectins. Intensifying research on the antiviral plant lectins, adopting a glyco-biotechnological approach, and with deeper insights into the "glycovirological" aspects may result in the designing of alternative and potent blueprints against the 21st century's biological pandemic of SARS-CoV-2 causing COVID-19.
Subject(s)
Antiviral Agents/therapeutic use , Biological Therapy/methods , COVID-19/prevention & control , Disease Eradication/methods , Plant Lectins/therapeutic use , SARS-CoV-2/drug effects , Animals , Antiviral Agents/isolation & purification , Antiviral Agents/pharmacology , Biological Therapy/trends , COVID-19/epidemiology , Disease Eradication/trends , Humans , Plant Lectins/isolation & purification , Plant Lectins/pharmacologyABSTRACT
Psoriasis is a common inflammatory skin disorder, which is mediated by the immune system and affects 1-4% of the world's population. Psoriasis is caused by a complex interaction between the immune system, autoantigens, psoriasis-associated genetic factors, and various environmental factors. As a chronic disease requiring long-term treatment, psoriasis is associated with follow-up costs and an economic burden on the patients, their families, and healthcare systems. The current treatments for moderate-to-severe plaque psoriasis include topical therapy, phototherapy, and systemic drugs consisting of biological/non-biological drugs. Within the past two decades, recent biological therapies for psoriasis have rapidly advanced. Moreover, new bispecific agents have the potential for better disease control, while small molecule drugs offer a future alternative to biological drugs and the more cost-effective, long-term treatment of the disease. The present study aimed to review updated data regarding the inhibitors used to improve plaque psoriasis that contain biologics, bispecific agents, small molecules, and aptamers (either approved or in the research phase).
Subject(s)
Biological Therapy/trends , Psoriasis/drug therapy , Skin/pathology , Animals , Autoimmunity , Gene-Environment Interaction , HumansABSTRACT
Various living organisms have proven to influence human health significantly, either in a commensal or pathogenic manner. Harnessing the creatures may remarkably improve human healthcare and cure the intractable illness that is challenged using traditional drugs or surgical approaches. However, issues including limited biocompatibility, poor biosafety, inconvenience for personal handling, and low patient compliance greatly hinder the biomedical and clinical applications of living organisms when adopting them for disease treatment. Microneedle arrays (MNAs), emerging as a promising candidate of biomedical devices with the functional diversity and minimal invasion, have exhibited great potential in the treatment of a broad spectrum of diseases, which is expected to improve organism-based therapies. In this review, we systemically summarize the technologies employed for the integration of MNAs with specific living organisms including diverse viruses, bacteria, mammal cells and so on. Moreover, their applications such as vaccination, anti-infection, tumor therapy and tissue repairing are well illustrated. Challenges faced by current strategies, and the perspectives of integrating more living organisms, adopting smarter materials, and developing more advanced technologies in MNAs for future personalized and point-of-care medicine, are also discussed. It is believed that the combination of living organisms with functional MNAs would hold great promise in the near future due to the advantages of both biological and artificial species.
Subject(s)
Biological Therapy/methods , Drug Delivery Systems/instrumentation , Drug Delivery Systems/methods , Administration, Cutaneous , Bacteria , Biological Therapy/trends , Cells , Immunotherapy/methods , Immunotherapy/trends , Needles , Skin/drug effects , Vaccination/methods , Vaccination/trends , VirusesABSTRACT
Multiple sclerosis (MS) is a neuroinflammatory disease in which unresolved and uncontrolled inflammation disrupts normal cellular homeostasis and leads to a pathological disease state. It has long been recognized that endogenously derived metabolic by-products of omega fatty acids, known as specialized pro-resolving lipid mediators (SPMs), are instrumental in resolving the pathologic inflammation. However, there is minimal data available on the functional status of SPMs in MS, despite the fact that MS presents a classical model of chronic inflammation. Studies to date indicate that dysfunction of the SPM biosynthetic pathway is responsible for their altered levels in patient-derived biofluids, which contributes to heightened inflammation and disease severity. Collectively, current findings suggest the contentious role of SPMs in MS due to variable outcomes in biological matrices across studies conducted so far, which could, in part, also be attributed to differences in population characteristics. It seems that SPMs have neuroprotective action on MS by exerting proresolving effects on brain microglia in its preclinical model; however, there are no reports demonstrating the direct effect of SPMs on oligodendrocytes or neurons. This reveals that "one size does not fit all" notion holds significance for MS in terms of the status of SPMs in other inflammatory conditions. The lack of clarity served as the impetus for this review, which is the first of its kind to summarize the relevant data regarding the role of SPMs in MS and the potential to target them for biomarker development and future alternative therapies for this disease. Understanding the mechanisms behind biological actions of SPMs as resolution mediators may prevent or even cure MS and other neurodegenerative pathologies.
Subject(s)
Biological Therapy/trends , Fatty Acids, Omega-3/metabolism , Fatty Acids, Omega-6/metabolism , Inflammation Mediators/metabolism , Inflammation/metabolism , Microglia/physiology , Multiple Sclerosis/metabolism , Animals , Autoimmunity , Humans , Inflammation/immunology , Inflammation/therapy , Multiple Sclerosis/immunology , Multiple Sclerosis/therapyABSTRACT
Atherosclerosis is a multifactorial disease influenced by genetics, lifestyle and environmental factors. Despite therapeutic advances that reduce the risk of cardiovascular events, atherosclerosis-related diseases remain the leading cause of mortality worldwide. Precise targeting of genes involved in lipoprotein metabolism is an emerging approach for atherosclerosis prevention and treatment. This article focuses on the latest developments, clinical potential and current challenges of monoclonal antibodies, vaccines and genome/transcriptome modification strategies, including antisense oligonucleotides, genome/base editing and gene therapy. Multiple lipid lowering biological therapies have already been approved by the FDA with impressive results to date, while many more promising targets are being pursued in clinical trials or pre-clinical animal models.
Subject(s)
Atherosclerosis/therapy , Biological Therapy/trends , Dyslipidemias/therapy , Animals , Atherosclerosis/epidemiology , Biological Therapy/methods , Dyslipidemias/epidemiology , Endocrinology/methods , Endocrinology/trends , Humans , Therapies, Investigational/methods , Therapies, Investigational/trendsABSTRACT
BACKGROUND: Anti-T2 biological therapies have proven to effectively reduce acute exacerbations and daily doses of oral steroids in severe eosinophilic asthma. Despite the remarkable clinical efficacy, there are usually only moderate improvements in airflow limitation, suggesting that other measures of lung function like small airway dysfunction (SAD) might better reflect the clinical response. We aimed to investigate if measures of small airway function would predict and correlate with the clinical response to anti-T2 therapy. METHODS: We studied data of patients who were previously included in the German prospective longitudinal All Age Asthma Cohort (ALLIANCE) that recruits asthma patients of all severity grades and inflammatory phenotypes. The selection criteria for this analysis were adult patients with severe eosinophilic asthma under treatment with anti-T2 biological agents. Asthma control was assessed by asthma control test (ACT) and number of severe exacerbations. Small airway function was assessed by the frequency dependence of resistance (FDR, R5-20)) derived from impulse oscillometry (IOS) and the mean forced expiratory flow between 25 and 75% of the forced vital capacity (FEF25-75). We also studied air trapping (RV and RV/TLC), blood eosinophils and FeNO. Patients were classified into responders and partial or non-responders. Clinical response was defined as at least 50% reduction in annualized severe exacerbations and daily oral steroid doses accompanied with a minimum increase of 3 points in the ACT score. We used a Receiver Operator Characteristic (ROC) to study the capacity of FDR in predicting clinical response compared to other clinical variable like blood eosinophils. We studied the correlation between FDR measures and clinical response, represented by the ACT score and number of exacerbations, using linear regressions. RESULTS: 20 patients were included (mean age, 59 ± 9 years; 60% female; mean body mass index (BMI), 27.6 ± 5.4 kg/m2; mean absolute blood eosinophils, 570 ± 389/µl; mean number of severe exacerbations 12 months prior to initiating the biological therapy, 5.0 ± 3; mean predicted FEV1, 76 ± 21%; mean predicted FDR, 224 ± 140%; mean daily prednisolone dose, 6.4 ± 4.9 mg; mean ACT score, 15 ± 5). Responders had significantly higher baseline FDR compared to partial or non-responders but similar FEV1, FEF25-75, RV and RV/TLC. ROC analysis showed that the combination of FDR and blood eosinophils had the best predictive capacity of the clinical response among all tested clinical markers (FeNO, FEV1, FDR, blood eosinophils) with an AUC of 85% [67-100%], (CI = 0.95, p = 0.01). Linear regressions indicated better associations between improvements in FDR and ACT score (R2 = 0.42, p = 0.001) than with FEV1 and ACT score (R2 = 0.25, p = 0.013). Likewise, we observed better associations between improvements in FDR and reduction of exacerbations (R2 = 0.41, p = 0.001) than with FEV1 (R2 = 0.20, p = 0.025). CONCLUSION: Our data suggest that severe SAD may represent a distinct phenotype of eosinophilic asthma that substantially improves under anti-T2 biological therapy. Measures of small airway function might be useful in selecting appropriate patients qualifying for anti-T2 biological therapy in addition to blood eosinophil count.
Subject(s)
Asthma/diagnosis , Asthma/drug therapy , Biological Therapy/methods , Pulmonary Eosinophilia/diagnosis , Pulmonary Eosinophilia/drug therapy , Severity of Illness Index , Aged , Antibodies, Monoclonal, Humanized/pharmacology , Antibodies, Monoclonal, Humanized/therapeutic use , Asthma/physiopathology , Biological Therapy/trends , Female , Forced Expiratory Volume/drug effects , Forced Expiratory Volume/physiology , Humans , Longitudinal Studies , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , Pulmonary Eosinophilia/physiopathology , Treatment OutcomeABSTRACT
INTRODUCTION: Atopic dermatitis (AD) is a chronic inflammatory skin condition characterized by erythematous lesions, pruritus, and a skin barrier defect. Long-term treatment in children is challenging, as there is only one Food and Drug Administration-approved systemic medication. Current treatments may have limited efficacy or serious side effects in children. With a deeper understanding of AD pathogenesis and the advent of target-specific medications, several biologics are undergoing clinical trials for future use in pediatric AD. AREAS COVERED: This article reviews the current and emerging biologic therapies for treatment of pediatric AD. It allows for comprehensive comparison of medications and their clinical trials to help providers optimize patient treatment plans while providing expert insight into upcoming advancements in the treatment of pediatric AD. EXPERT OPINION: Treating pediatric AD is complicated given the variety of disease severity, psychosocial impact, and relative lack of approved medications for severe disease. Given the safety data on dupilumab, newer biologics will likely be second-line. We do not yet understand the long-term impact of newer biologics on an immature immune system, nor do we fully understand their risks and toxicities. We should proceed optimistically, yet cautiously, with the study of biologics in children.
Subject(s)
Biological Products/therapeutic use , Biological Therapy/trends , Dermatitis, Atopic/drug therapy , Pediatrics/trends , Therapies, Investigational/trends , Age of Onset , Antibodies, Monoclonal/therapeutic use , Biological Therapy/methods , Child , Dermatitis, Atopic/epidemiology , Drug Delivery Systems , Humans , Pediatrics/methods , Severity of Illness Index , Therapies, Investigational/methods , United States/epidemiologySubject(s)
Biological Therapy , Colitis, Ulcerative , Congenital Abnormalities , Crohn Disease , Infant, Newborn, Diseases , Pregnancy Complications , Adult , Biological Therapy/statistics & numerical data , Biological Therapy/trends , Cohort Studies , Colitis, Ulcerative/epidemiology , Congenital Abnormalities/classification , Congenital Abnormalities/diagnosis , Congenital Abnormalities/epidemiology , Crohn Disease/epidemiology , Crohn Disease/therapy , Female , Humans , Infant, Newborn , Infant, Newborn, Diseases/classification , Infant, Newborn, Diseases/diagnosis , Infant, Newborn, Diseases/epidemiology , Pregnancy , Pregnancy Complications/epidemiology , Pregnancy Complications/therapy , Pregnancy Outcome/epidemiology , Risk Assessment/methods , Risk Assessment/statistics & numerical data , Risk FactorsABSTRACT
The activation of the cGAS-STING pathway has tremendous potential to improve anti-tumor immunity by generating type I interferons. In recent decades, we have witnessed that producing dsDNA upon various stimuli is an initiative factor, triggering the cGAS-SING pathway for a defensive host. The understanding of both intracellular cascade reaction and the changes of molecular components gains insight into type I IFNs and adaptive immunity. Based on the immunological study, the STING-cGAS pathway is coupled to cancer biotherapy. The most challenging problem is the limited therapeutic effect. Therefore, people view 5, 6-dimethylxanthenone-4-acetic acid, cyclic dinucleotides and various derivative as cGAS-STING pathway agonists. Even so, these agonists have flaws in decreasing biotherapeutic efficacy. Subsequently, we exploited agonist delivery systems (nanocarriers, microparticles and hydrogels). The article will discuss the activation of the cGAS-STING pathway and underlying mechanisms, with an introduction of cGAS-STING agonists, related clinical trials and agonist delivery systems.
Subject(s)
Carcinogenesis/genetics , Membrane Proteins/genetics , Neoplasms/genetics , Nucleotidyltransferases/genetics , Biological Therapy/trends , Carcinogenesis/immunology , Humans , Immunotherapy/trends , Interferon Type I/genetics , Neoplasms/immunology , Neoplasms/pathology , Neoplasms/therapy , Signal Transduction/genetics , Xanthines/therapeutic useABSTRACT
Este trabajo tiene como objetivo revisar las contribuciones de la biotecnología, en relación con el tratamiento, diagnóstico y la monitorización de la enfermedad renal crónica (ERC) y sus comorbilidades más frecuentes, especialmente la anemia. En relación con los tratamientos, enfocamos el desarrollo de productos biofarmacéuticos como los agentes estimulantes de la eritropoyesis (ESA), que fueron los primeros biofármacos utilizados para el tratamiento de la anemia asociada a la ERC; analizamos sus características y utilización actual después de varios años de experiencia clínica, así como también otras alternativas en desarrollo. Revisamos distintos tipos de bioterapias, la utilización de las células estromales mesenquimales de médula ósea (MSC) y tratamientos alternativos con modificaciones dietarias, que se basan en la asociación entre la microbiota intestinal de los pacientes renales crónicos y sus condiciones fisiopatológicas. Finalmente, en relación con el diagnóstico y monitorización, nos referimos al estudio y validación de biomarcadores diagnósticos, predictivos y terapéuticos que han permitido optimizar los resultados clínicos en este tipo de pacientes. (AU)
The aim of this work is to review the contributions of biotechnology, in relation to the treatment, diagnosis and monitoring of chronic kidney disease (CKD) and its most frequent comorbidities, especially anemia. Regarding the treatment, we focus on the development of biopharmaceutical products such as erythropoiesis stimulating agents (ESA), which were the first biopharmaceuticals used to treat anemia associated with chronic kidney disease (CKD). We analyzed their characteristics and their current use after several years of clinical experience, as well as other alternatives in development. We also review different types of biotherapies, the use of bone marrow mesenchymal stromal cells (MSC) and alternative treatments with dietary modifications, which are based on the association between the intestinal microbiota of chronic kidney patients and their pathophysiological conditions. Finally, in relation to diagnosis and monitoring, we refer to the study and validation of diagnostic, predictive and therapeutic biomarkers that have made clinical results possible to be optimized in this type of patient. (AU)
Subject(s)
Humans , Biological Therapy/trends , Renal Insufficiency, Chronic/therapy , Quality of Life , Biotechnology , Biomarkers , Erythropoietin/deficiency , Probiotics/therapeutic use , Mesenchymal Stem Cell Transplantation/trends , Erythropoiesis/drug effects , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/diet therapy , Renal Insufficiency, Chronic/rehabilitation , Prebiotics/classification , Glycoside Hydrolase Inhibitors/therapeutic use , Gastrointestinal Microbiome , Hematinics/administration & dosage , Hematinics/pharmacology , Hematinics/pharmacokinetics , Anemia/diagnosis , Anemia/etiology , Anemia/drug therapyABSTRACT
Asthma is a chronic and heterogenic respiratory tract disorder with a high global prevalence. The underlying chronic inflammatory process and airway remodeling (AR) contribute to the symptomatology of the disease. The most severely ill asthma patients may now be treated using a variety of monoclonal antibodies aiming key inflammatory cytokines involved in asthma pathogenesis. Although clinical data shows much beneficial effects of biological therapies in terms of reduction of exacerbation rates, improvement of lung functions, asthma control and patients' quality of life, little is known on the effects of these monoclonal antibodies on AR-a key clinical trait of long-term asthma management. In this review, the authors summarize the data on the proven effects of monoclonal antibodies in asthma on AR. To date, in terms of reversing AR, the mostly studied was omalizumab. However, some studies also addressed this clinical issue in context of other severe asthma biological therapies (mepolizumab, benralizumab, tralokinumab). Still, data on effects of particular biological therapies on AR in severe asthma are incomplete and require further studies. According to the American Thoracic Society research recommendations, future research shall focus on AR in asthma and improve drugs targeting AR, including the available and future monoclonal antibodies.
Subject(s)
Airway Remodeling , Asthma/pathology , Asthma/therapy , Biological Therapy/methods , Airway Remodeling/drug effects , Airway Remodeling/immunology , Anti-Asthmatic Agents/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Asthma/immunology , Biological Therapy/trends , HumansABSTRACT
Eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss syndrome) is the least frequent antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV). Major advances of our knowledge on its pathophysiology have revealed features of both AAV and eosinophilic disorders. The development of targeted biotherapies for both diseases opened new possibilities for EGPA management. In this review, we highlight the rationale underlying the routine treatment strategy, which relies mainly on corticosteroids, with immunosuppressant adjunction for severe disease. However, novel therapies are still needed for refractory/relapsing disease and to alleviate the corticosteroid-dependence of asthma and chronic rhinosinusitis. At present, the most promising biotherapies target either eosinophil biology, like mepolizumab, an anti-interleukin-5, or the B-cell compartment, with rituximab. Recent clinical data on new treatment options are discussed and therapeutic strategies are proposed.
Subject(s)
Churg-Strauss Syndrome/therapy , Adrenal Cortex Hormones/therapeutic use , Antibodies, Antineutrophil Cytoplasmic/adverse effects , Antibodies, Monoclonal, Humanized/therapeutic use , Biological Therapy/methods , Biological Therapy/trends , Churg-Strauss Syndrome/pathology , Glucocorticoids/therapeutic use , Granulomatosis with Polyangiitis/pathology , Granulomatosis with Polyangiitis/therapy , Humans , Immunosuppressive Agents/therapeutic use , Rituximab/therapeutic useABSTRACT
BACKGROUND: Asthma is a common and potentially serious condition affecting 300 million people worldwide. For many years, we have relied on a one-size-fits-all approach to its management, using corticosteroids and bronchodilators for all symptomatic patients. However, with more recent advances, it has become clear that asthma is a heterogeneous condition with multiple different underlying pathways. Understanding the different subtypes will be a key to giving us the ability to intervene in a targeted way to personalize care for patients with asthma. SOURCES OF DATA: Key published literature, guidelines and trials from clinicaltrials.gov. AREAS OF AGREEMENT: The most widely studied of these subtypes is T2 high eosinophilic asthma, for which there are an increasing number of biologic therapies available. T2 high asthma is associated with the cytokines interleukin (IL)-4, IL-5 and IL-13, for each of which biologics have been developed. AREAS OF CONTROVERSY: It is currently unclear which of the available biologics provides superior efficacy. It is also unclear how to select which biologic for which patient. GROWING POINTS: Head-to-head trials of the available T2 biologics will be important to determine superiority, and a suggested order for trialling biologics. Going further than this, we would like to see further analyses of available biologics to allow us to predict responders from non-responders in advance of administering therapy. AREAS TIMELY FOR DEVELOPING RESEARCH: Non-eosinophilic T2 low asthma is an area that is under-researched and for which there are few treatments available. It is likely that there are different subtypes in this category of asthma and unravelling what these are will be crucial to developing effective treatments.
Subject(s)
Asthma , Biological Therapy , Molecular Targeted Therapy , Precision Medicine/trends , Asthma/classification , Asthma/immunology , Asthma/physiopathology , Asthma/therapy , Biological Therapy/methods , Biological Therapy/trends , Clinical Trials as Topic , Drug Discovery , Genetic Heterogeneity , Humans , Molecular Targeted Therapy/methods , Molecular Targeted Therapy/trends , Pulmonary Eosinophilia/immunology , Research Design , Respiratory Hypersensitivity/immunologySubject(s)
Asthma/therapy , Biological Therapy/methods , Bronchi/physiopathology , Adult , Biological Therapy/trends , HumansABSTRACT
The presentation, pathobiology, and prognosis of asthma are highly heterogeneous and challenging for clinicians to diagnose and treat. In addition to the adaptive immune response that underlies allergic inflammation, innate immune mechanisms are increasingly recognized to be critical mediators of the eosinophilic airway inflammation present in most patients with asthma. Efforts to classify patients by severity and immune response have identified a number of different clinical and immune phenotypes, indicating that the innate and adaptive immune responses are differentially active among patients with the disease. Advances in the detection of these subgroups using clinical characteristics and biomarkers have led to the successful development of targeted biologics. This has moved us to a more personalized approach to managing asthma. Here we review the emerging endotypes of asthma and the biologics that have been developed to treat them.
Subject(s)
Adrenal Cortex Hormones/therapeutic use , Asthma/genetics , Asthma/therapy , Biological Therapy/trends , Cytokines/metabolism , Asthma/diagnosis , Asthma/immunology , Biological Therapy/methods , Bronchial Provocation Tests , Bronchodilator Agents/therapeutic use , Bronchoscopy/methods , Female , Forecasting , Humans , Male , Prognosis , Respiratory Function Tests , Risk Assessment , Severity of Illness Index , Treatment OutcomeABSTRACT
Food allergy prevalence has increased over the past 2 decades and is estimated to affect 8% of children and 4% to 10% of adults. There is an unmet need to evaluate new therapeutic modalities that may decrease the risk of food-induced anaphylaxis and improve patients' quality of life. Oral, epicutaneous, and sublingual food immunotherapies have different safety and efficacy profiles, and their long-term outcome and applicability are unclear. Food allergy trials are currently evaluating different biologics (given as monotherapy or adjunct to immunotherapy), modified food proteins, DNA vaccines, and fecal microbiota transplantation.
Subject(s)
Biological Therapy/trends , Feces/microbiology , Food Hypersensitivity/therapy , Microbiota/immunology , Vaccines, DNA/immunology , Animals , Antibodies, Monoclonal, Humanized/therapeutic use , Fecal Microbiota Transplantation , Humans , Omalizumab/therapeutic useABSTRACT
Antibacterial resistance is a great concern and requires global action. A critical question is whether enough new antibacterial drugs are being discovered and developed. A review of the clinical antibacterial drug pipeline was recently published, but comprehensive information about the global preclinical pipeline is unavailable. This Review focuses on discovery and preclinical development projects and has found, as of 1 May 2019, 407 antibacterial projects from 314 institutions. The focus is on Gram-negative pathogens, particularly bacteria on the WHO priority bacteria list. The preclinical pipeline is characterized by high levels of diversity and interesting scientific concepts, with 135 projects on direct-acting small molecules that represent new classes, new targets or new mechanisms of action. There is also a strong trend towards non-traditional approaches, including diverse antivirulence approaches, microbiome-modifying strategies, and engineered phages and probiotics. The high number of pathogen-specific and adjunctive approaches is unprecedented in antibiotic history. Translational hurdles are not adequately addressed yet, especially development pathways to show clinical impact of non-traditional approaches. The innovative potential of the preclinical pipeline compared with the clinical pipeline is encouraging but fragile. Much more work, focus and funding are needed for the novel approaches to result in effective antibacterial therapies to sustainably combat antibacterial resistance.
Subject(s)
Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/pharmacology , Biological Therapy/trends , Drug Discovery/trends , Drug Evaluation, Preclinical/trends , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/drug therapy , Drug Resistance, Bacterial , Treatment OutcomeABSTRACT
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