Authors:
R. Draghia-Akli, A.M. Bodles-Brakhop, A.S. Khan, M.A. Pope, and P.A. Brown
Summary:
Growth hormone-releasing hormone (GHRH) plasmid-based therapy to treat companion dogs with spontaneous malignancies and cachexia-associated anemia receiving a cancer-specific treatment was examined in a double-blinded, placebo-controlled trial. Preliminary studies in our laboratory have demonstrated that this therapy could be effective in treating anemia and cachexia and their related disorders in cancer and aging. In the current study, dogs (age 10.51 2.5 years, weight 24.88 12.9 kg) received a single 0.35 mg dose of plasmid or placebo intramuscularly followed by electroporation, and hematological, biochemical and hormonal parameters, as well as quality of life were analyzed up to 120 days post-treatment. Post-hoc study analysis revealed that GHRH-treated dogs could be categorized into responders and non-responders. Response rate was defined as a 5% or greater increase above the nadir in red blood cell count, hemoglobin and hematocrit. Analysis of the GHRH-treated group showed that responder dogs survived 84% longer, 178 26 days post-treatment, while non-responders and placebo controls survived 95 16 and 97 31 days post-treatment, respectively. Insulin-like growth factor-I levels increased in treated dogs with a significant percentage change from baseline at day 60 (55.76% 12.06, p=0.02) and positively correlated with body weight, hematological parameters and improved protein metabolism. The increases in hematological parameters (RBCs, hemoglobin and hematocrit) were significantly higher (p<0.01) in GHRH responders as compared to non-responders and placebo-treated animals. Examination of 10 quality of life parameters revealed that the GHRH plasmid-treated dogs improved compared to the untreated controls. GHRH treated dogs demonstrated significant increases in appetite and alertness, while adverse effects linked to cancer-specific therapy, such as vomiting and diarrhea decreased. This study shows that plasmid-based therapy could be an effective and efficient method for reversing cachexia-associated anemia in patients, while increasing their chance of survival during specific cancer therapy. Overall, the beneficial effects of a growth hormone releasing hormone plasmid-based therapy on cancer-afflicted subjects are substantial and provide evidence that this therapy should be examined in a human trial.
Source:
The Endocrine Society; 11:00 AM, Exhibit Halls B/C, 06/16/08