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Therapeutic bispecific antibodies cross the blood-brain barrier in nonhuman primates. | LitMetric

AI Article Synopsis

  • * Researchers developed bispecific antibodies that target β-secretase (BACE1) and bind to the transferrin receptor (TfR), allowing them to successfully cross the BBB and reduce brain amyloid-β (Aβ) in mice.
  • * Experiments in humanized mice and monkeys showed that these anti-TfR/BACE1 antibodies effectively reduced Aβ in both brain tissue and cerebrospinal fluid, proving the TfR platform's ability to deliver treatments across the BBB in primates.

Article Abstract

Using therapeutic antibodies that need to cross the blood-brain barrier (BBB) to treat neurological disease is a difficult challenge. We have shown that bispecific antibodies with optimized binding to the transferrin receptor (TfR) that target β-secretase (BACE1) can cross the BBB and reduce brain amyloid-β (Aβ) in mice. Can TfR enhance antibody uptake in the primate brain? We describe two humanized TfR/BACE1 bispecific antibody variants. Using a human TfR knock-in mouse, we observed that anti-TfR/BACE1 antibodies could cross the BBB and reduce brain Aβ in a TfR affinity-dependent fashion. Intravenous dosing of monkeys with anti-TfR/BACE1 antibodies also reduced Aβ both in cerebral spinal fluid and in brain tissue, and the degree of reduction correlated with the brain concentration of anti-TfR/BACE1 antibody. These results demonstrate that the TfR bispecific antibody platform can robustly and safely deliver therapeutic antibody across the BBB in the primate brain.

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Source
http://dx.doi.org/10.1126/scitranslmed.3009835DOI Listing

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