Gene therapy by electroporation for the treatment of chronic renal failure in companion animals.
BACKGROUND
Growth hormone-releasing hormone (GHRH) plasmid-based therapy for the treatment of chronic renal failure and its complications was examined. Companion dogs (13.1+/-0.8 years, 29.4+/-5.01 kg) and cats (13.2+/-0.9 years, 8.5+/-0.37 kg) received a single 0.4 mg or 0.1 mg species-specific plasmid injection, respectively, intramuscularly followed by electroporation, and analyzed up to 75 days post-treatment; controls underwent electroporation without plasmid administration.


RESULTS
Plasmid-treated animals showed an increase in body weight (dogs 22.5% and cats 3.2%) compared to control animals, and displayed improved quality of life parameters including significant increases in appetite, activity, mentation and exercise tolerance levels. Insulin-like growth factor I (IGF-I, the downstream effector of GHRH) levels were increased in the plasmid treated animals. Hematological parameters were also significantly improved. Protein metabolism changes were observed suggesting a shift from a catabolic to an anabolic state in the treated animals. Blood urea nitrogen and creatinine did not show any significant changes suggesting maintenance of kidney function whereas the control animal's renal function deteriorated. Treated animals survived longer than control animals with 70% of dogs and 80% of cats surviving until study day 75. Only 17% and 40% of the control dogs and cats, respectively, survived to day 75.


CONCLUSIONS
Improved quality of life, survival and general well-being indicate that further investigation is warranted, and show the potential of a plasmid-based therapy by electroporation in preventing and managing complications of renal insufficiency.
Brown
Patricia A
PA
VGX Animal Health, 2700 Research Forest Drive, Suite 180, The Woodlands, Texas 77381, USA. pbrown@vgxah.com
Bodles-Brakhop
Angela M
AM
Pope
Melissa A
MA
Draghia-Akli
Ruxandra
R
D000375:Aging; D000818:Animals; D001806:Blood Urea Nitrogen; D001835:Body Weight; D002415:Cats; D003404:Creatinine / Q000097:blood; D004285:Dogs; D018274:Electroporation / Q000662:veterinary; D015316:Genetic Therapy / Q000662:veterinary*; D013007:Growth Hormone-Releasing Hormone / Q000235:genetics / Q000627:therapeutic use; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007501:Iron / Q000097:blood; D007676:Kidney Failure, Chronic / Q000097:blood / Q000235:genetics / Q000628:therapy / Q000662:veterinary*; D010957:Plasmids / Q000008:administration & dosage; D011506:Proteins / Q000378:metabolism
D011506:Proteins; D007334:Insulin-Like Growth Factor I; D013007:Growth Hormone-Releasing Hormone; D003404:Creatinine; D007501:Iron