A5073300619- Monoclonal and Polyclonal Antibodies Research
- CAR-T cell therapy research
- Virus-based gene therapy research
- T-cell and B-cell Immunology
- S100 Proteins and Annexins
- Lysosomal Storage Disorders Research
- Glycosylation and Glycoproteins Research
- Immune Cell Function and Interaction
- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- Cardiac Imaging and Diagnostics
- Cancer Immunotherapy and Biomarkers
- Chronic Lymphocytic Leukemia Research
- Retinal Development and Disorders
- Inflammatory mediators and NSAID effects
- Neurogenetic and Muscular Disorders Research
- Immune Response and Inflammation
- Synthesis and Biological Evaluation
- RNA regulation and disease
- Galectins and Cancer Biology
- HIV-related health complications and treatments
- Neonatal Respiratory Health Research
- Retinal Diseases and Treatments
- Chronic Myeloid Leukemia Treatments
- Cardiovascular Function and Risk Factors
Regenxbio (United States)
2019-2024
AstraZeneca (United States)
2020-2021
Imperial College London
2008-2015
The London College
2012
Dartmouth–Hitchcock Medical Center
2011
Hammersmith Hospital
2008
GlaxoSmithKline (Italy)
2008
Roche (Switzerland)
1999-2005
La Roche College
1999-2005
University of Tennessee Health Science Center
2005
There has been great progress in ocular gene therapy, but delivery of viral vectors to the retinal pigmented epithelium (RPE) and retina can be challenging. Subretinal injection, preferred route for most applications, requires a surgical procedure that risks. Herein we report novel therapy approach, suprachoroidal injection AAV8 vectors, which is less invasive could done an outpatient setting. Two weeks after AAV8.GFP rats, GFP fluorescence covered 18.9% RPE flat mounts extended entirely...
Recent studies in non-human primates administered recombinant adeno-associated viruses (rAAVs) have shown lesions the dorsal root ganglia (DRG) of unknown pathogenesis. In this study, rAAV9s manufactured using different purification methods alongside a non-expressing Null AAV9 vector was to groups cynomolgus monkeys followed by neuropathological evaluation after 4 weeks. Lesions, including neuronal degeneration, increased cellularity, and nerve fiber were observed DRG, regardless methods....
Unregulated inflammation underlies many diseases, including sepsis. Much interest lies in targeting anti-inflammatory mechanisms to develop new treatments. One such target is the protein annexin A1 (AnxA1) and its receptor, FPR2/ALX. Using intravital videomicroscopy, we investigated role of AnxA1 FPR2/ALX a murine model endotoxin-induced cerebral [intraperitoneal injection lipopolysaccharide (LPS)]. An inflammatory response was confirmed by elevations proinflammatory serum cytokines,...
Abstract Ligation of OX40 (CD134, TNFRSF4) on activated T cells by its natural ligand (OX40L, CD252, TNFSF4) enhances cellular survival, proliferation, and effector functions such as cytokine release cytotoxicity. We engineered a recombinant human OX40L IgG4P Fc fusion protein termed MEDI6383 that assembles into hexameric structure exerts potent agonist activity following engagement OX40. displayed solution-phase was enhanced when the clustered gamma receptors (FcγRs) surface adjacent cells....
Background MEDI6012 is recombinant human lecithin cholesterol acyltransferase, the rate-limiting enzyme in reverse transport. Infusions of acyltransferase have potential to enhance transport and benefit patients with coronary heart disease. The purpose this study was test safety, pharmacokinetic, pharmacodynamic profile MEDI6012. Methods Results This phase 2a double-blind randomized 48 subjects stable disease on a statin single dose or placebo (6:2) (NCT02601560) ascending doses administered...
Although a disease-modifying therapy for classic late infantile neuronal ceroid lipofuscinosis (CLN2 disease) exists, poor understanding of cellular pathophysiology has hampered the development more effective and persistent therapies. Here, we investigated nature progression neurological underlying neuropathological changes in Cln2R207X mice, which carry one most common pathogenic mutations human patients but are yet to be fully characterized. Long-term electroencephalography recordings...
Hypothalamo-pituitary-adrenocortical dysfunction contributes to morbidity and mortality in a high proportion of patients with sepsis. Here, we provide new insights into the underlying adrenal pathology. Using murine model endotoxemia (LPS injection), demonstrate that insufficiency is triggered early disease. LPS induced local inflammatory response gland within 4 hours administration, coupled increased expression mRNAs for annexin A1 (AnxA1) formyl peptide receptors [(Fprs) 1, 2, 3], loss...
Objective To determine the correlation between ritonavir (RTV) dose and degree of enhancement saquinavir (SQV) exposure. Methods Combined analysis pharmacokinetic data at steady state obtained from two open‐label, randomized, parallel‐group, multiple‐dose, single‐centre studies involving healthy volunteers. Plasma samples for SQV assay were 97 subjects following multiple dosing a range (400–1800 mg) plus RTV (100–400 dosages 13–14 days. The pharmacokinetics derived by model‐independent,...
Objective Our objective was to characterize population pharmacokinetics of enfuvirtide, 90 mg twice daily injected subcutaneously, in treatment-experienced human immunodeficiency virus type 1 (HIV-1)–infected patients, as well the relationship between exposure and antiviral effect. Methods Plasma concentrations enfuvirtide HIV-1 ribonucleic acid were obtained from 628 patients 2 phase III studies. NONMEM software used for pharmacokinetic analysis assess effects age, gender, body weight,...
Abstract Exenatide, a glucagon‐like peptide‐1 receptor agonist was originally developed as either twice daily or once weekly injectable therapeutic for patients with type 2 diabetes. Exenatide QW suspension use an autoinjector device, in which the microspheres are suspended Miglyol 812, mixture of medium chain triglycerides (MCTs). MCTs class lipids whose fatty acid chains contain from six to 12 carbon atoms (medium acids MCFAs). While edible oils present many foods, including foodstuffs...
Mucopolysaccharidosis type I (MPS I) is a rare metabolic disorder caused by deficiency of α-L-iduronidase (IDUA), resulting in glycosaminoglycan (GAG) accumulation and multisystemic disease. Current treatments include hematopoietic stem cell transplantation enzyme replacement therapy, but these do not address all manifestations the We infused MPS mice with an adeno-associated virus 9 (AAV9)-IDUA vector (RGX-111) at doses from 10
A novel automated computer imaging technique for assessing motor activity in rats to a standard acceptable regulatory neurotoxicity studies is described. The Ethovision video tracking, motion analysis, and behavior recognition system shown reliably assess both increases decreases of treated with D-amphetamine sulfate or chlorpromazine hydrochloride, respectively, by demonstrating statistically significant treatment-related effects each drug. It also has advantages over existing beam-breaking...
3056 Background: OX40 is a tumor necrosis factor receptor found primarily on activated T effector (Teff) cells and regulatory (Treg) including lymphocytes infiltrating mouse human tumors. Costimulation of by agonist molecules hypothesized to improve antitumor immunity enhancing Teff cell activity inhibiting Treg suppression. MEDI6383 novel, agonist, ligand fusion protein currently undergoing early phase clinical testing for the treatment advanced solid malignancies. Methods: Preclinical...
Introduction: Left ventricular (LV) thrombus formation is a recognized complication in patients with anterior STEMI. Warfarin often used this setting to prevent despite limited data support practice. We sought determine the incidence of LV and assess clinical benefit anticoagulation for prophylaxis against ischemic stroke presenting STEMI reduced ejection fraction (EF) who were treated early reperfusion therapies dual antiplatelet agents. Methods: Consecutive (N=298) low post-infarct EF...