SCH 412499: biodistribution and safety of an adenovirus containing P21(WAF-1/CIP-1) following subconjunctival injection in Cynomolgus monkeys.
Monkey studies were conducted for the preclinical safety assessment of SCH 412499, an adenovirus encoding p21, administered by subconjunctival injection prior to trabeculectomy for postoperative maintenance of the surgical opening. Biodistribution of SCH 412499 was minimal and there was no systemic toxicity. Findings included swollen, partially closed or shut eye(s) and transient congestion in the conjunctiva. A mononuclear cell infiltrate was present in the conjunctiva, choroid and other ocular tissues, but completely or partially resolved over time. Electroretinograms and visual evoked potentials revealed no adverse findings. Thus, the findings are not expected to preclude the clinical investigation of SCH 412499.
Veneziale
Robert W
RW
Drug Safety, Schering-Plough Research Institute. Lafayette, New Jersey 07848-0032, USA. robert.veneziale@spcorp.com
Bral
Christopher M
CM
Sinha
Dinesh P
DP
Watkins
Robert W
RW
Cartwright
Mark E
ME
Rosenblum
Irwin Y
IY
Treinen
Kimberley A
KA
Kishnani
Narendra S
NS
Nelson
Joyce
J
Chen
Zoe
Z
Faha
Barbara
B
Maneval
D
D
Munger
Robert J
RJ
Cai
Xiao-Yan
XY
Cullen
Constance
C
Arezzo
Joseph C
JC
D000256:Adenoviridae / Q000235:genetics*; D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D003228:Conjunctiva; D003231:Conjunctivitis / Q000473:pathology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics*; D004596:Electroretinography; D004797:Enzyme-Linked Immunosorbent Assay; D005074:Evoked Potentials, Visual / Q000502:physiology; D005123:Eye / Q000473:pathology; D005260:Female; D015316:Genetic Therapy; D020327:Glaucoma Drainage Implants; D006339:Heart Rate / Q000502:physiology; D007267:Injections; D008252:Macaca fascicularis; D008297:Male; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution; D014129:Trabecular Meshwork; D014945:Wound Healing
D050759:Cyclin-Dependent Kinase Inhibitor p21