Mihalis S. Kariolis

This study shows the PD-risk GBA1 variant E326K reduces lysosomal GCase activity by disrupting LIMP2 interaction and causes lysosomal and mitochondrial dysfunction.

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

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.

This study shows that reduced progranulin leads to increased legumain activity, which promotes TDP-43 pathology in FTLD, suggesting legumain as a therapeutic target.

Peripheral AAV-mediated delivery of brain-penetrant PGRN rescues TDP-43 pathology, neurodegeneration and motor phenotypes in FTLD-GRN models.

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.