Extensive neuroprotection by choroid plexus transplants in excitotoxin lesioned monkeys.
Huntington's disease (HD) results from degeneration of striatal neurons. Choroid plexus (CP) cells secrete neurotrophic factors, and CP transplants are neuroprotective in rat models of HD. To determine if similar neuroprotective effects could be obtained in primates, porcine CP was encapsulated in alginate capsules. PCR confirmed that the CP cells expressed transthyretin and immunocytochemistry demonstrated typical ZO-1 and tubulin staining. In vitro, CP conditioned media enhanced the survival and preserved neurite number and length on serum deprived neurons. Cynomolgus primates were transplanted with CP-loaded capsules into the caudate and putamen followed by quinolinic acid (QA) lesions 1 week later. Control monkeys received empty capsules plus QA. Choroid plexus transplants significantly protected striatal neurons as revealed by stereological counts of NeuN-positive neurons (8% loss vs. 43% in controls) and striatum volume (10% decrease vs. 40% in controls). These data indicate that CP transplants might be useful for preventing the degeneration of neurons in HD.
Emerich
Dwaine F
DF
LCT BioPharma, Providence, RI 02906, USA. ed3fjm@aol.com
Thanos
Christopher G
CG
Goddard
Moses
M
Skinner
Stephen J M
SJ
Geany
Marilyn S
MS
Bell
William J
WJ
Bintz
Briannan
B
Schneider
Patricia
P
Chu
Yaping
Y
Babu
Rangasamy Suresh
RS
Borlongan
Cesario V
CV
Boekelheide
Kim
K
Hall
Susan
S
Bryant
Bronwyn
B
Kordower
Jeffrey H
JH
D000818:Animals; D016380:Brain Tissue Transplantation; D002831:Choroid Plexus / Q000187:drug effects / Q000473:pathology*; D004195:Disease Models, Animal; D006816:Huntington Disease / Q000473:pathology*; D007150:Immunohistochemistry; D008252:Macaca fascicularis; D018696:Neuroprotective Agents; D009498:Neurotoxins / Q000633:toxicity*; D051381:Rats; D013552:Swine
D018696:Neuroprotective Agents; D009498:Neurotoxins