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Drug delivery

Apolipoprotein E (APOE)-derived peptide for drug delivery across the blood brain barrier (BBB)

In vitro and mouse studies suggest an APOE-derived peptide could help deliver therapeutics across the BBB. In vitro assays identified two peptides derived from APOE that bound low-density lipoprotein-related protein 1 a-2-macroglobulin receptor (LRP1; CD91), a receptor on the BBB surface, and underwent transcytosis. In a mouse model for the lysosomal storage disease mucopolysaccharidosis I (MPS I), which involves loss of a-l-iduronidase (IDUA) function in the CNS, delivery of transgenes encoding a fusion between the APOE-derived peptide and IDUA increased levels of the enzyme in the brain compared with delivery of transgenes encoding a control peptide-IDUA fusion. Next steps include testing the effects on neurological deficits in additional animal models of MPS I.
Angiochem Inc. has LRP1-binding peptide-enzyme fusions in preclinical development to treat lysosomal storage disorders.

SciBX 6(8); doi:10.1038/scibx.2013.204
Published online Feb. 28, 2013

Patent application filed; available for licensing

Wang, D. et al. Proc. Natl. Acad. Sci. USA; published online Feb. 4, 2013;
Contact: Dao Pan, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio

Contact: Roscoe O. Brady, National Institutes of Health, Bethesda, Md.