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| DOGS
WITH CANCER
Anemia and cachexia are frequent complications associated
with late stage cancer, often to the point of precluding further
therapy. We conducted a pre-clinical trial in which we enrolled
severely debilitated companion dogs with naturally occurring
tumors. All of the dogs enrolled in the study, including controls,
were also on specific chemotherapy and/or radiotherapy. The
treated animals received a single intramuscular injection
of a plasmid expressing a Growth Hormone Releasing Hormone
(GHRH) analog with a long half-life, immediately followed
by a short electroporation procedure. Anemia resolved post-treatment,
as indicated by significant increases in mean red blood cell
count, hematocrit and hemoglobin concentrations, in addition
to a significant rise in the percentage of circulating lymphocytes.
Treated dogs maintained their weights over the 56 day study
and did not show any adverse effects from the treatment. Furthermore,
beneficial effects on the quality-of-life, increases in weight,
activity level, exercise tolerance, appetite and hematological
parameters of the treated dogs lasted for more than a year
post-treatment.
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These results provided support for the use of GHRH-expressing plasmids
in the treatment of anemia and cachexia associated with cancer in
dogs. Further studies are planned.
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DOGS
WITH RENAL FAILURE
Studies have shown that Growth Hormone (GH) and IGF-I improves
renal function in human patients with renal failure.
In veterinary applications, current therapy for chronic
renal failure (CRF)-associated anemia in dogs is
erythropoietin (EPO) of human origin, and more a recently
experimentally, a canine recombinant EPO. Effective response
to human EPO decreases over time due to the formation of antibodies,
and the canine EPO while successful in treating anemia still
has some negative side effects.
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A single intramuscular dose of a plasmid expressing GHRH, immediately
followed by short electroporation procedure was given to dogs with
CRF. The dogs had a clinically determined life expectancy of 90 days
with blood urea nitrogen (BUN) value of > 25 mg/dl or creatinine
value of > 1.6 mg/dl. After a 75 day follow up body weight
increased from 10% to 20%, plasma IGF-I levels increased, circulating
iron concentrations almost doubled in treated dogs and, most importantly,
several hematological parameters, including red blood cells, hematocrit
and hemoglobin were significantly improved as early as day 20 post-treatment.
Kidney function, as measured by BUN and creatinine was maintained
throughout the study.
These results provided support for the use of GHRH-expressing plasmids
in the treatment of anemia associated with CRF in dogs. Further studies
in a larger population are planned.
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