Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 May:184:114234.
doi: 10.1016/j.addr.2022.114234. Epub 2022 Mar 17.

Blood-brain barrier delivery for lysosomal storage disorders with IgG-lysosomal enzyme fusion proteins

William M Pardridge  1
Affiliations
Free article
Review

Blood-brain barrier delivery for lysosomal storage disorders with IgG-lysosomal enzyme fusion proteins

William M Pardridge. Adv Drug Deliv Rev. 2022 May.
Free article

Abstract

The majority of lysosomal storage diseases affect the brain. Treatment of the brain with intravenous enzyme replacement therapy is not successful, because the recombinant lysosomal enzymes do not cross the blood-brain barrier (BBB). Biologic drugs, including lysosomal enzymes, can be re-engineered for BBB delivery as IgG-enzyme fusion proteins. The IgG domain of the fusion protein is a monoclonal antibody directed against an endogenous receptor-mediated transporter at the BBB, such as the insulin receptor or the transferrin receptor. This receptor transports the IgG across the BBB, in parallel with the endogenous receptor ligand, and the IgG acts as a molecular Trojan horse to ferry into brain the lysosomal enzyme genetically fused to the IgG. The IgG-enzyme fusion protein is bi-functional and retains both high affinity binding for the BBB receptor, and high lysosomal enzyme activity. IgG-lysosomal enzymes are presently in clinical trials for treatment of the brain in Mucopolysaccharidosis.

Keywords: Cerebrospinal fluid; Drug targeting; Endothelium; Fusion proteins; Mathematical model; Receptor-mediated transport.

PubMed Disclaimer

Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

MeSH terms

LinkOut - more resources