Pascal E. Sanchez

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

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.

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.

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.