Delivery of enzymes and neurotrophic proteins to treat CNS disorders
W. Pan, A.J. Kastin
Pennington Biomedical Research Center, LSU Systems, Baton Rouge, Louisiana 70808, USA
Regeneration of the central nervous system (CNS) encounters the
obstacles of inefficient delivery and degradation of neurotrophic
molecules when used as therapeutic reagents. Although the blood-brain
barrier (BBB) prevents free permeation of enzymes and neurotrophic
proteins, it permits selective permeation of certain peptides and
proteins by way of specific transport systems. Here, two scenarios are
presented: delivery of lysosome enzymes to treat lysosomal storage
diseases affecting the brain, and delivery of neurotrophins and
neurophic peptides to rescue neuronal cell death after CNS trauma and
secondary degeneration. The goals are to determine the pharmacokinetics
of these proteins after peripheral delivery by intravenous injection,
to identify the mechanisms of transport, and to effectively enhance BBB
penetration by use of the transport systems present at the cerebral
endothelial cells. Regulation of the transport systems in pathological
conditions and by pharmacological manipulation, therefore, can exert a
significant impact in the treatment of CNS disorders.
Key words:
blood-brain barrier; neurotrophic protein; cytokine; transport; neuroregeneration
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