A5034662634- Neuroinflammation and Neurodegeneration Mechanisms
- Immunotherapy and Immune Responses
- Radiopharmaceutical Chemistry and Applications
- Monoclonal and Polyclonal Antibodies Research
- Immune Response and Inflammation
- Adipokines, Inflammation, and Metabolic Diseases
- Drug Transport and Resistance Mechanisms
- Immune cells in cancer
- Atherosclerosis and Cardiovascular Diseases
- Barrier Structure and Function Studies
- Diet and metabolism studies
- Thermal Regulation in Medicine
- Alzheimer's disease research and treatments
- Photoacoustic and Ultrasonic Imaging
- Neuroscience and Neuropharmacology Research
- S100 Proteins and Annexins
- Multiple Sclerosis Research Studies
- Neurological Disease Mechanisms and Treatments
- RNA Interference and Gene Delivery
- Neuropeptides and Animal Physiology
- Ultrasound and Hyperthermia Applications
- Chemical Synthesis and Analysis
- Click Chemistry and Applications
- Inflammation biomarkers and pathways
- Amino Acid Enzymes and Metabolism
Denali Therapeutics (United States)
2023-2024
Stanford Medicine
2019-2023
Stanford University
2017-2020
Abstract Loss-of-function variants of TREM2 are associated with increased risk Alzheimer’s disease (AD), suggesting that activation this innate immune receptor may be a useful therapeutic strategy. Here we describe high-affinity human TREM2-activating antibody engineered monovalent transferrin (TfR) binding site, termed transport vehicle (ATV), to facilitate blood–brain barrier transcytosis. Upon peripheral delivery in mice, ATV:TREM2 showed improved brain biodistribution and enhanced...
Brain exposure of systemically administered biotherapeutics is highly restricted by the blood-brain barrier (BBB). Here, we report engineering and characterization a BBB transport vehicle targeting CD98 heavy chain (CD98hc or SLC3A2) heterodimeric amino acid transporters (TVCD98hc). The pharmacokinetic biodistribution properties CD98hc antibody (ATVCD98hc) are assessed in humanized knock-in mice cynomolgus monkeys. Compared to most existing platforms transferrin receptor, peripherally...
Abstract Neuroinflammation is a hallmark of ischemic stroke, which leading cause death and long‐term disability. Understanding the exact cellular signaling pathways that initiate propagate neuroinflammation after stroke will be critical for developing immunomodulatory therapies. In particular, precise mechanisms inflammatory in clinically relevant hyperacute period, hours have not been elucidated. We used RiboTag technique to obtain microglia astrocyte‐derived mRNA transcripts (4 h) acute (3...
Neuroinflammation plays a key role in neuronal injury after ischemic stroke. PET imaging of translocator protein 18 kDa (TSPO) permits longitudinal, noninvasive visualization neuroinflammation both preclinical and clinical settings. Many TSPO tracers have been developed, however, it is unclear which tracer the most sensitive accurate for monitoring vivo spatiotemporal dynamics across applications. Hence, there need head-to-head comparisons promising different disease states. Accordingly, aim...
Ischemic stroke provokes a neuroinflammatory response and simultaneously promotes release of epinephrine norepinephrine by the sympathetic nervous system. This increased outflow can act on β2-adrenergic receptors expressed immune cells such as brain-resident microglia monocyte-derived macrophages (MDMs), but effect post-stroke neuroinflammation is unknown. Thus, we investigated how changes in signaling after onset influence microglia/MDM response, specific importance to neuroinflammation. To...
B lymphocytes are a key pathologic feature of multiple sclerosis (MS) and becoming an important therapeutic target for this condition. Currently, there is no approved technique to noninvasively visualize cells in the central nervous system (CNS) monitor MS disease progression response therapies. Here, we evaluated <sup>64</sup>Cu-rituximab, radiolabeled antibody specifically targeting human cell marker CD20, its ability image mouse model using PET. <b>Methods:</b> To CNS infiltration by...
Rationale: Localized blood-brain barrier (BBB) opening can be achieved with minimal to no tissue damage by applying pulsed focused ultrasound alongside a low microbubble (MB) dose. However, relatively little is known regarding how varying treatment parameters affect the degree of neuroinflammation following BBB opening. The goal this study was evaluate activation an inflammatory response as function applied acoustic pressure using two different doses. Methods: Mice were treated 650 kHz peak...
Abstract Background B cells play a central role in multiple sclerosis (MS) through production of injurious antibodies, secretion pro-inflammatory cytokines, and antigen presentation. The therapeutic success monoclonal antibodies (mAbs) targeting some but not all individuals suffering from MS highlights the need for method to stratify patients monitor response treatments real-time. Herein, we describe development first CD19 positron emission tomography (PET) tracer, its evaluation rodent...
Neuroinflammation is a hallmark of ischemic stroke, which leading cause death and long-term disability. Understanding the exact cellular signaling pathways that initiate propagate neuroinflammation after stroke will be critical for developing immunomodulatory therapies. In particular, precise mechanisms inflammatory in clinically relevant hyperacute period, hours have not been elucidated. We used RiboTag technique to obtain astrocyte microglia-derived mRNA transcripts (4 hours) acute (3...
Abstract Transferrin receptor (TfR)-mediated transcytosis across the blood-brain barrier (BBB) is a promising strategy to improve delivery of biologics central nervous system (CNS). However, it remains unclear whether age and aging-related diseases impact TfR expression and/or BBB transport capacity. Here, we used TfR-targeted antibody vehicle (ATV ) enhance CNS in healthy mice 5xFAD mouse model Alzheimer’s disease (AD). Healthy neonates exhibited highest vascular ATV brain exposure, whereas...
Abstract Background: B cells play a central role in multiple sclerosis (MS) through production of injurious antibodies, secretion pro-inflammatory cytokines, and antigen presentation. The therapeutic success monoclonal antibodies (mAbs) targeting some but not all individuals suffering from MS highlights the need for method to stratify patients monitor response treatments real time. Herein, we describe development first CD19 positron emission tomography (PET) tracer its evaluation rodent...
People who are obese 64% more likely to have a stroke than those not. Obesity is also associated with chronic peripheral inflammation characterized by increased antigen presentation and pro-inflammatory T lymphocytes. The influence of obesity-induced on outcomes has not been well studied. We hypothesized that similar mechanism might drive detrimental after in mice lead worse outcomes. fed 60% kCal high fat diet for six or fifteen weeks measured the neuroinflammatory response stroke. verified...