Delivery of Biologics Across the Blood–Brain Barrier with Molecular Trojan Horse Technology

  title={Delivery of Biologics Across the Blood–Brain Barrier with Molecular Trojan Horse Technology},
  author={William M. Pardridge},
Biologics are potential new therapeutics for many diseases of the central nervous system. Biologics include recombinant lysosomal enzymes, neurotrophins, decoy receptors, and therapeutic antibodies. These are large molecule drugs that do not cross the blood–brain barrier (BBB). All classes of biologics have been tested, without success, in clinical trials of brain disease over the last 25 years. In none of these past clinical trials was the biologic re-engineered to enable transport across the… 

Blood-Brain Barrier and Delivery of Protein and Gene Therapeutics to Brain

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

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Targeted delivery of protein and gene medicines through the blood–brain barrier

  • W. Pardridge
  • Biology
    Clinical pharmacology and therapeutics
  • 2015
Certain peptidomimetic monoclonal antibodies that target endogenous receptors on the BBB, such as the insulin or transferrin receptor, enable the re‐engineering of biologic drugs that cross theBBB.

Engineering and expression of a chimeric transferrin receptor monoclonal antibody for blood–brain barrier delivery in the mouse

The genetic engineering, expression, and validation of a chimeric TfRMAb with high activity for the mouse TfR is described, which can be used in future engineering of therapeutic fusion proteins for BBB drug delivery in the mouse.

Drug Targeting of Erythropoietin Across the Primate Blood-Brain Barrier with an IgG Molecular Trojan Horse

A novel IgG-EPO fusion protein has been engineered, expressed, and shown to be bifunctional with retention of high-affinity binding to both the insulin and EPO receptors.

Addressing Safety Liabilities of TfR Bispecific Antibodies That Cross the Blood-Brain Barrier

It is reported that when mice were dosed with therapeutic TfR antibodies, the animals showed acute clinical reactions and a reduction in immature red blood cells, known as reticulocytes, which suggest that the blood-brain barrier is not the only obstacle to surmount on the way to the brain, at least when using TFR as a molecular lift.