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. 2009 Jan 16;9:4.
doi: 10.1186/1472-6750-9-4.

Gene Therapy by Electroporation for the Treatment of Chronic Renal Failure in Companion Animals

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Free PMC article

Gene Therapy by Electroporation for the Treatment of Chronic Renal Failure in Companion Animals

Patricia A Brown et al. BMC Biotechnol. .
Free PMC article

Abstract

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.

Conclusion: 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.

Figures

Figure 1
Figure 1
IGF-I levels in cats and dogs with chronic renal failure treated with plasmid-mediated GHRH therapy. The results are presented as means ± SEM. (A). 75% of GHRH-treated cats have increased IGF-I levels at 20–75 days after GHRH treatment (* P < 0.05). (B). 75% of GHRH-treated dogs have increased IGF-I levels at 20–75 days after GHRH treatment (* P < 0.05).
Figure 2
Figure 2
Circulating iron concentration in GHRH-treated dogs. The results are presented as means ± SEM. Circulating iron concentration is significantly improved in dogs treated with plasmid-mediated GHRH (where * P < 0.05).
Figure 3
Figure 3
Protein metabolism in cats with chronic renal failure treated with plasmid-mediated GHRH therapy. The results are presented as means ± SEM. Protein metabolism is significantly improved in cats treated with plasmid-mediated GHRH (where * P < 0.05) whereas control cats do not show any significant differences over the time points measured.
Figure 4
Figure 4
BUN and Creatinine levels and ratio for GHRH-treated dogs and cats. The results are presented as means ± SEM. The BUN (A) and creatinine (B) levels remained unchanged for the GHRH-treated dogs while control animals displayed an increase in BUN and creatinine at 75 days compared to day 0. (C) The BUN/creatinine ratio in cats was not significantly altered in the GHRH-treated animals but control cats showed an increase at day 75 compared to day 0.

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