Destruction of choroid plexus cells in vitro: a new concept for the treatment of hydrocephalus?
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.


CONCLUSIONS
These results suggest that immunotoxin-mediated ablation of choroid plexus may be a viable method of treating hydrocephalus and choroid plexus-derived tumors.
Timothy
Jake
J
Department of Neurosurgery, Leeds General Infirmary, Leeds, England.
Chumas
Paul
P
Chakrabarty
Aruna
A
Drake
James M
JM
Morrison
Ewan
E
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D002478:Cells, Cultured; D002831:Choroid Plexus / Q000187:drug effects* / Q000473:pathology; D016545:Choroid Plexus Neoplasms / Q000473:pathology; D004847:Epithelial Cells / Q000187:drug effects*; D006801:Humans; D006849:Hydrocephalus / Q000188:drug therapy* / Q000473:pathology; D000922:Immunotoxins / Q000494:pharmacology*; D066298:In Vitro Techniques; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D051381:Rats; D012276:Ricin / Q000494:pharmacology*; D012756:Sheep
D000922:Immunotoxins; D012276:Ricin