| 摘要 |
The blood-brain barrier (BBB) is a formidable obstacle preventing efficient delivery
of therapeutic agents to the central nervous system (CNS). High peripheral dosing of
CNS drugs often leads to unwanted systemic side effects. Direct introduction of
therapeutic molecules into the CNS can bypass the BBB, but limited diffusion,
metabolism, and capillary clearance confine their effective range. An emerging
technology, convection-enhanced delivery (CED), successfully overcomes these
barriers to disseminate CNS therapies. CED utilizes the principle of continuous
interstitial macromolecular infusion with a positive pressure gradient through
surgically-implanted microcatheters to safely target CNS lesions. The following CEDbased
anti-tumor therapies are being investigated in clinical trials: 1) recombinant
immunotoxins or bacterial toxins specifically targeted to tumor cell surface molecules
(interleukin-immunotoxin, transferrin-diphtheria toxin), 2) viral thymidine kinase
gene that cooperatively act with the chemotherapy agent, gancyclovir. CED can also
introduce anti-infection drugs, metabolic agents to stimulate or ablate functional
brain domains, and has the potential to be an effective and versatile technology for
delivering future therapies in treating neurodegenerative diseases via stem cell or
other novel strategies. |
