Abstract
BackgroundGrowth 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.ResultsPlasmid-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.ConclusionImproved 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.
Highlights
Growth hormone-releasing hormone (GHRH) plasmid-based therapy for the treatment of chronic renal failure and its complications was examined
Chronic renal failure (CRF) can affect the growth hormone releasing hormone/growth hormone/insulin-like growth factor-I (GHRH/GH/IGF-I) axis [5] which can lead to growth retardation in children and is associated with increased morbidity and mortality [6,7]
By day 75, only 40% (n = 6 out of 15) of the control cats were still alive whereas 80% (n = 24 out of 30) of the GHRHtreated cats survived; only 17% (n = 2 out of 12) of the control dogs survived until day 75 whereas 70% (n = 21 out of 30) of the GHRH-treated dogs survived
Summary
Growth hormone-releasing hormone (GHRH) plasmid-based therapy for the treatment of chronic renal failure and its complications was examined. Chronic renal failure (CRF) can affect the growth hormone releasing hormone/growth hormone/insulin-like growth factor-I (GHRH/GH/IGF-I) axis [5] which can lead to growth retardation in children and is associated with increased morbidity and mortality [6,7]. The action of GH and its mediator, IGF-I, on body composition, protein, glucose, and bone metabolism offers real therapeutic options for these patients, including the improvement of the catabolic state in adults with end-stage renal failure. Existing treatments for conditions associated with renal failure, such as anemia, wasting, immune dysfunction, or other conditions have some significant drawbacks: the daily injection routine is impractical and often associated with local or systemic adverse effects and may lead to non-compliance in patients
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