Timothy Earr

Dual targeting of transferrin receptor and CD98hc enhances brain exposure of large molecules

This paper demonstrates that dual targeting of TfR and CD98hc enhances brain exposure of large molecules compared to single-target approaches.

Transferrin receptor-mediated transport at the blood-brain barrier is elevated in early development but maintained across adult aging

This study investigates TfR-mediated BBB transport in mice across development and aging, finding elevated transport in early development and stability across adulthood, including in an AD model.

Engineering anti-amyloid antibodies with transferrin receptor targeting improves brain biodistribution and mitigates ARIA

This study develops an antibody transport vehicle targeting the transferrin receptor to improve brain delivery of anti-amyloid antibodies, reducing ARIA-like lesions and vascular inflammation in a mouse model.

DNL343 is an investigational CNS penetrant eIF2B activator that prevents and reverses the effects of neurodegeneration caused by the Integrated Stress Response

DNL343 reduces neurodegeneration in mouse models by inhibiting the integrated stress response and normalizing dysregulated biomarkers, with potential clinical relevance for vanishing white matter disease.

Targeting Transferrin Receptor to Transport Antisense Oligonucleotides Across the Blood-Brain Barrier

This paper demonstrates that systemically delivered OTV, a TfR-binding molecule, effectively transports ASO across the BBB, achieving widespread and sustained knockdown of target genes in the CNS of mice and non-human primates.

Molecular architecture determines brain delivery of a transferrin-receptor targeted lysosomal enzyme

The paper compares brain delivery and efficacy of two TfR-targeted enzyme fusions in MPS II mice, finding the moderate-affinity ETV:IDS has better brain exposure and substrate reduction than the high-affinity IgG:IDS.

Fibrillar Aβ causes profound microglial metabolic perturbations in a novel APP knock-in mouse model

This paper characterizes microglial metabolic changes in an APP knock-in mouse model of AD, finding lipid dysregulation and immunometabolic perturbations linked to fibrillar Aβ.