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🧠 5–8× brain delivery (mice)

Daily news that is actually intellectually stimulating.

Author

Anthony Ao
August 13, 2025

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Engineered antibody ferries Alzheimer’s drug deeper into the brain—and eases ARIA‑like effects—in mice

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Researchers from Denali Therapeutics and Biogen report an antibody “transport vehicle” that targets the transferrin receptor (TfR) to carry an anti‑amyloid‑β (Aβ) antibody across the blood–brain barrier. The engineered construct (ATV^{cisLALA}:Aβ) uses asymmetrical Fc mutations to reduce TfR‑related hematology liabilities while preserving effector function. In mouse studies, it achieved 5–8× higher brain concentrations than conventional anti‑Aβ antibodies, showed broader parenchymal distribution with less buildup around vessels, and predominantly crossed via capillaries—changes that coincided with markedly fewer ARIA‑like lesions and reduced vascular inflammation.

Why it matters

Anti‑amyloid antibodies (e.g., aducanumab, lecanemab, donanemab) can slow decline but have limited brain delivery and can trigger ARIA, a key safety concern seen on MRI. By improving delivery and shifting where the antibody distributes in brain tissue, this TfR‑guided approach may offer a path to better balancing efficacy and safety. These findings are preclinical (in mice); confirmation in humans will be essential.

ELI5 Summary

  • The brain has a tough security gate (the blood‑brain barrier). Current Alzheimer’s antibodies don’t get in well and can pile up near blood vessels, sometimes causing swelling or tiny bleeds on scans (called ARIA).

  • Scientists added a “ride‑along pass” to an anti‑amyloid antibody so it can use a natural door on blood vessels (the transferrin receptor) to cross into the brain.

  • In mice, this brought 5–8× more antibody into brain tissue, spread it out more evenly (mainly via tiny capillaries), and sharply reduced ARIA‑like changes and vessel inflammation.

  • It’s early, mouse‑only research; whether it works safely in people still needs testing.

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Stay curious,
Anthony Ao
The PhDLevel Team
☕️🐻 Powered by caffeine & curiosity

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