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Destruction of choroid plexus cells in vitro: a new concept
for the treatment of hydrocephalus
Timothy J, Chumas P, Chakrabarty A, Drake JM, Morrison E
Department of Neurosurgery, Leeds General Infirmary, Leeds, England.
Objective. The current treatment of hydrocephalus using ventriculoperitoneal
shunts and third ventriculostomies remains problematic.
We revisited the concept
of destruction of the choroid plexus for the treatment of hydrocephalus by using
an immunotoxin-based technique to specifically destroy this tissue.
This
approach was based on the observation that, as an epithelial tissue, choroid
plexus expresses a number of specific cell-surface proteins that represent
excellent potential targets for the creation of a choroid plexus-specific
immunotoxin.
Methods. In this study, we characterized sheep and human choroid
plexus cells (including atypical and carcinoma cell lines) using fluorescence
microscopy in combination with histochemical staining of rat brain and confirmed
the presence of a number of epithelium-specific proteins in choroid plexus
cells.
Immunotoxins were then manufactured by linking these antibodies to ricin
A chain and ricin A-B chain.
These immunotoxins were delivered to choroid
plexus-derived cells in culture, and the results were compared with results of
exposure to a nonspecific immunotoxin.
Results. Complete cell death of choroid
plexus cells was seen after only a 1-hour exposure to the specific immunotoxin,
as opposed to the minimal cell death seen with a nonspecific immunotoxin after
several hours of exposure.
Conclusion. These results suggest that
immunotoxin-mediated ablation of choroid plexus may be a viable method of
treating hydrocephalus and choroid plexus-derived tumors.
PMID: 15028150 [PubMed - indexed for MEDLINE]
Source: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15028150
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