A5069014298- Psoriasis: Treatment and Pathogenesis
- T-cell and B-cell Immunology
- Monoclonal and Polyclonal Antibodies Research
- Asthma and respiratory diseases
- Immunodeficiency and Autoimmune Disorders
- Urticaria and Related Conditions
- Autoimmune and Inflammatory Disorders Research
- Cytokine Signaling Pathways and Interactions
- Rheumatoid Arthritis Research and Therapies
- Spondyloarthritis Studies and Treatments
- Autoimmune Bullous Skin Diseases
- IL-33, ST2, and ILC Pathways
- Dermatology and Skin Diseases
- Immune Cell Function and Interaction
- Neuroscience and Neuropharmacology Research
- Colorectal and Anal Carcinomas
- Toxin Mechanisms and Immunotoxins
- Hormonal and reproductive studies
- Hidradenitis Suppurativa and Treatments
- Ion channel regulation and function
- Receptor Mechanisms and Signaling
- Neurotransmitter Receptor Influence on Behavior
- Immunotherapy and Immune Responses
- HER2/EGFR in Cancer Research
- Inhalation and Respiratory Drug Delivery
Costello Medical Consulting (United Kingdom)
2025
UCB Pharma (United Kingdom)
2014-2024
University College Birmingham
2012-2024
UCB Pharma (Belgium)
2014
Royal Berkshire NHS Foundation Trust
2014
Tufts University
2014
Celltechgen (United States)
2004
National Institute of Environmental Health Sciences
1986-1988
Objective Interleukin (IL)-17A has emerged as pivotal in driving tissue pathology immune-mediated inflammatory diseases. The role of IL-17F, sharing 50% sequence homology and overlapping biological function, remains less clear. We hypothesised that together with IL-17A, contributes to chronic inflammation, dual neutralisation may lead more profound suppression inflammation than inhibition IL-17A alone. Methods Preclinical experiments assessed the IL-17F using disease-relevant human cells. A...
Hidradenitis suppurativa (HS) is a chronic inflammatory disease with high burden for patients and limited existing therapeutic options.To evaluate the efficacy safety of bimekizumab, monoclonal IgG1 antibody that selectively inhibits interleukin 17A 17F in individuals moderate to severe HS.This phase 2, double-blind, placebo-controlled randomized clinical trial an active reference arm was performed from September 22, 2017, February 21, 2019. The study included 2- 4-week screening period,...
Aims To assess safety, pharmacokinetics (PK) and clinical efficacy of bimekizumab (formerly UCB4940), a novel humanized monoclonal antibody dual inhibitor interleukin (IL)‐17A IL‐17F, in subjects with mild plaque psoriasis. Methods Randomized, double‐blind, first‐in‐human study 39 who received single‐dose intravenous (8–640 mg) or placebo (NCT02529956). Results Bimekizumab demonstrated dose‐proportional linear PK was tolerated across the dose range assessed. No subject discontinued due to...
Interleukin (IL)-17A is a key driver of inflammation and the principal target anti-IL-17 therapeutic monoclonal antibodies. IL-17A, its structurally similar family member IL-17F, have been shown to be functionally dysregulated in certain human immune-mediated inflammatory diseases such as psoriasis, psoriatic arthritis axial spondyloarthritis. Given overlapping biology these two cytokines, we postulated that dual neutralization IL-17A IL-17F may provide greater depth clinical response...
Rozanolixizumab (UCB7665), a humanized high-affinity anti-human neonatal Fc receptor (FcRn) monoclonal antibody (IgG4P), has been developed to reduce pathogenic IgG in autoimmune and alloimmune diseases. We document the isolation compare rozanolixizumab with same variable region expressed various mono-, bi- trivalent formats. report activity data for different molecular formats human cells, FcRn-transgenic mice, cynomolgus monkeys. Rozanolixizumab, considered most effective format,...
Background Chronic lung diseases are the third leading cause of death in United States due part to an incomplete understanding pathways that govern progressive tissue remodeling occurs these disorders. Adenosine is elevated lungs animal models and humans with chronic disease where it promotes air-space destruction fibrosis. signaling increases production pro-fibrotic cytokine interleukin-6 (IL-6). Based on observations, we hypothesized IL-6 contributes a model adenosine levels elevated....
Interleukin-6 (IL-6) is a critical regulator of the immune system and has been widely implicated in autoimmune disease. Here, we describe discovery characterization olokizumab, humanized antibody to IL-6. Data from structural biology, cell biology primate pharmacology demonstrate therapeutic potential targeting IL-6 at "Site 3", blocking interaction with signaling co-receptor gp130.
IL-23 is considered a critical regulator of IL-17 in Th17 cells; however, its requirement for inducing production other human immune subsets remains incompletely understood. Mucosal associated invariant T (MAIT) cells uniformly express retinoic acid receptor-related orphan receptor gamma t (RORγt) but only minor population have been shown to produce IL-17A. Here we show that IL-17F the dominant isoform produced by MAIT cells, not For optimal cell derived IL-17A and production, (TCR)...
Bimekizumab is a monoclonal antibody that selectively inhibits both interleukin (IL)-17A and IL-17F, which currently under investigation for treatment of moderate-to-severe plaque psoriasis. Maintenance dosing every 4 weeks well established with IL-17 inhibitors psoriasis.To investigate the possible interval during bimekizumab maintenance therapy to maintain clear skin, inform phase III studies.Forty-nine patients psoriasis received 320 mg at 0/4, followed week 16 by (n = 17) or placebo 32)....
Evaluate the efficacy and safety of dual neutralisation interleukin (IL)-17A IL-17F with bimekizumab, a monoclonal IgG1 antibody, in addition to certolizumab pegol (CZP) patients rheumatoid arthritis (RA) inadequate response (IR) pegol.During this phase 2a, double-blind, proof-of-concept (PoC) study (NCT02430909), moderate-to-severe RA received open-label CZP 400 mg at Weeks 0, 2 4, 200 Week 6. Patients IR 8 (Disease Activity Score 28-joint count C-reactive protein (DAS28(CRP))>3.2) were...
Objectives Interleukin (IL)-17 signalling has been shown to be a key regulator of disease in ankylosing spondylitis (AS) with several IL-17 blockers currently clinically approved. Despite this, the role bone pathology is poorly understood. This study aimed investigate context pathological formation. Methods A biomimetic human periosteum-derived cell (hPDC) model osteogenic differentiation was used combination recombinant cytokines, T-cell supernatants or serum from patients AS. IL-17A,...
The efficacy and tolerability of the imidazopyridine hypnotic, zolpidem, were investigated in 119 elderly psychiatric inpatients complaining insomnia a double-blind, parallel-group, placebo-controlled trial. After 7-day placebo washout period, patients randomized to receive 10 or 20 mg/day for 21 days; thereafter, all received 7 days. Sleep was assessed by patient observation on days 0, 1, 7, 14, 21, 22 28. Compared with placebo, zolpidem significantly improved total duration sleep between...
Interleukin‐6 (IL‐6) is implicated in the pathophysiology of several inflammatory conditions. Olokizumab, a humanized anti‐IL‐6 monoclonal antibody, selectively blocks final assembly IL‐6 signaling complex. A randomized, double‐blind, placebo‐controlled, phase I dose‐escalation study assessed safety and tolerability escalating single doses olokizumab administered intravenously (iv) or subcutaneously (sc) to 67 healthy male volunteers. The pharmacokinetics, pharmacodynamics immunogenicity...
An immune response is essential for protection against infection, but, in many individuals, aberrant responses self tissues cause autoimmune diseases such as rheumatoid arthritis (RA). How to diminish the while not augmenting infectious risk a challenge. Modern targeted therapies anti-TNF or anti-CD20 antibodies ameliorate disease, but at cost of some increase risk. Approaches that might specifically reduce autoimmunity and tissue damage without would be important. Here we describe TNF...
The delta isoform of phosphoinositide 3-kinase (PI3Kδ) regulates various lymphocyte functions. Considering the key pro-inflammatory role IL-17A and IL-17F cytokines in psoriasis spondyloarthritis (SpA), we investigated potential PI3Kδ blockade to suppress IL-17A, associated that could synergize with IL-17F. Using vitro studies primary human cells ex vivo inflamed target tissues, assessed if seletalisib, a selective inhibitor, suppresses cytokine production by T innate-like lymphocytes,...
Rationale: IL-13 is an important cytokine implicated in the pathogenesis of allergic asthma and attractive target for inhaled therapeutic.Objective: To investigate efficacy CDP7766, a nebulized anti–IL-13 monoclonal antibody Fab fragment, model cynomolgus macaques naturally sensitized to Ascaris suum.Methods: CDP7766 was using vibrating-membrane nebulizer on basis eFlow technology. The aerosol generated analyzed determine particle size profile biophysical functional properties CDP7766....
Abstract Using a mouse mutagenesis screen, we have identified CD83 as being critical for the development of CD4+ T cells and their function postactivation. CD11c+ dendritic develop normally in mice with mutated gene but cell is substantially reduced. Additionally, now show that those mutant animal fail to respond following allogeneic stimulation. This at least part due an altered cytokine expression pattern characterized by increased production IL-4 IL-10 diminished IL-2 production. Thus,...
Steroid hormones, such as glucocorticoids (GC), influence immune and inflammatory responses through their suppressive actions. Recent evidence suggests that another steroid hormone, dehydroepiandrosterone (DHEA), provides an immunostimulatory opposing the effect of GC. DHEA circulates in its inactive sulphated form, DHEAS, requiring conversion to by a sulphatase (SS) enzyme for biological activity. Therefore, inhibition SS activity may affect responses, allowing endogenous GC effects...