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The prevalence of dementia in the Western world in people over the age of 60 has been estimated to be greater than 5%, about two-thirds of which are due to Alzheimer's disease. The age-specific prevalence of Alzheimer's disease nearly doubles every 5 years after age 65, leading to a prevalence of greater than 25% in those over the age of 90 (ref. 3). Here,(More)
Antibodies to transferrin receptor (TfR) have potential use for therapeutic entry into the brain. We have shown that bispecific antibodies against TfR and β-secretase (BACE1 [β-amyloid cleaving enzyme-1]) traverse the blood-brain barrier (BBB) and effectively reduce brain amyloid β levels. We found that optimizing anti-TfR affinity improves brain exposure(More)
The blood-brain barrier (BBB) poses a major challenge for developing effective antibody therapies for neurological diseases. Using transcriptomic and proteomic profiling, we searched for proteins in mouse brain endothelial cells (BECs) that could potentially be exploited to transport antibodies across the BBB. Due to their limited protein abundance, neither(More)
Automatically mining protein pathway information from the vast amount of published literature has been an increasing need from the pharmaceutical industry and biomedical research community. This task has been proved to be a formidable one. Many systems have been implemented, but few are practical. Some are too restricted and some are overly ambitious. 1(More)
In the developing brain, initial neuronal projections are formed through extensive growth and branching of developing axons, but many branches are later pruned to sculpt the mature pattern of connections. Despite its widespread occurrence, the mechanisms controlling pruning remain incompletely characterized. Based on pharmacological and biochemical analysis(More)
To compare the pharmacokinetics (PK) of MNRP1685A, a human monoclonal antibody (mAb) against neuropilin-1 (NRP1), in mice, rats, monkeys, and cancer patients from a Phase I study to model with parallel linear and nonlinear clearances. Binding characteristics of MNRP1685A in different species were evaluated using surface plasmon resonance technology. PK(More)
The development of bispecific antibodies as therapeutic agents for human diseases has great clinical potential, but broad application has been hindered by the difficulty of identifying bispecific antibody formats that exhibit favorable pharmacokinetic properties and ease of large-scale manufacturing. Previously, the development of an antibody technology(More)
T he human genome project, with its goal of genome-wide sequencing, has generated extensive information. For example, the project has examined three gigabytes of human genomic DNA and predicts that approximately 30,000 genes exist in the human genome. The challenge now is to determine a gene's function and role in biological pathways. With this information,(More)
The spread of tau pathology correlates with cognitive decline in Alzheimer's disease. In vitro, tau antibodies can block cell-to-cell tau spreading. Although mechanisms of anti-tau function in vivo are unknown, effector function might promote microglia-mediated clearance. In this study, we investigated whether antibody effector function is required for(More)
Automatically mining protein pathway information from the vast amount of published literature has been an increasing need from the pharmaceutical industry and biomedical research community. This task has been proved to be a formidable one. Many systems have been implemented, but few are practical. Some are too restricted and some are overly ambitious. This(More)