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Cited by 152Barrier Structure and Function StudiesDrug Transport and Resistance MechanismsNanoparticle-Based Drug Delivery

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

Pardridge, William M.·2017·BioDrugs
DOI 10.1007/s40259-017-0248-z
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Abstract

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 BBB. If the biologic does not cross the BBB, the drug cannot reach the target site in brain, and success in a clinical trial is not expected. Biologics can be re-engineered for BBB transport with the use of molecular Trojan horse technology. A BBB molecular Trojan horse is a monoclonal antibody (MAb) against an endogenous BBB receptor transporter, such as the insulin receptor or transferrin receptor. The receptor-specific MAb penetrates the brain via transport on the endogenous BBB receptor. The MAb acts as a molecular Trojan horse to deliver across the BBB the biologic pharmaceutical that is genetically fused to the MAb. The lead Trojan horse is a MAb against the human insulin receptor (HIR), and HIRMAb-derived fusion proteins have entered clinical trials for the treatment of brain disease.

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Crossref · 10.1007/s40259-017-0248-z

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  • The molecular Trojan horse approach relies on receptor-specific monoclonal antibodies or peptides to ferry genetically fused cargo into the brain.

    “The molecular Trojan horse approach, relying on the receptor-specific monoclonal antibodies or peptides to ferry the genetically fused cargo into the brain, is promising in delivery of biologics across the BBB.”

    From Neurotransmitter-derived lipidoids (NT-lipidoids) for enhanced brain delivery through intravenous injection (2020) · cites this paper as [17]

  • The molecular Trojan horse manufacturing process needs to be tailored specifically for each different biologic cargo, and stability, safety, and immunogenicity are challenges to clinical development.

    “However, the manufacturing process needs to be tailored specifically for each for different biologic cargo, and the stability, safety, and immunogenicity are challenges to clinical development (17).”

    From Neurotransmitter-derived lipidoids (NT-lipidoids) for enhanced brain delivery through intravenous injection (2020) · cites this paper as [17]

  • The molecular Trojan horse approach is promising for delivery of biologics across the blood-brain barrier.

    “The molecular Trojan horse approach, relying on the receptor-specific monoclonal antibodies or peptides to ferry the genetically fused cargo into the brain, is promising in delivery of biologics across the BBB.”

    From Neurotransmitter-derived lipidoids (NT-lipidoids) for enhanced brain delivery through intravenous injection (2020) · cites this paper as [17]

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Authors
Pardridge, W. M.
Affiliations
ArmaGen (United States) (US)
Corresponding author
Pardridge, William M.
ORCID
Pardridge, William M.
Venue
BioDrugs
Publisher
Springer Science and Business Media LLC
Published
2017-10-24
Volume
31
Issue
6
Pages
503-519
ISSN
  • 1172-7039 (ISSN-L)
  • 1173-8804
  • 1179-190X
DOI
10.1007/s40259-017-0248-z
OpenAlex
W2766410563
Cited by
152
References
11
Citations by year
2026: 2 · 2025: 14 · 2024: 11 · 2023: 17 · 2022: 22 · 2021: 30 · 2020: 24 · 2019: 13 · 2018: 18 · 2017: 1
FWCI
1.47
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (unspecified)
Locations
  • BioDrugs (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
Keywords
blood-brain barrier, biologics, insulin receptor, transferrin receptor, monoclonal antibodies, receptor-mediated transport, fusion protein, central nervous system disorders, neurotrophins, therapeutic antibodies, brain drug delivery
MeSH terms
Animals, Antibodies, Monoclonal, Biological Products, Biological Transport, Blood-Brain Barrier, Humans, Insulin-Like Growth Factor II, Receptor, Insulin, Receptors, Transferrin, Recombinant Fusion Proteins, Protein Engineering, Antigens, CD, Drug Delivery Systems

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