Thursday, February 28, 2013
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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;
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.
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,
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