Effects of plasmid-mediated growth hormone-releasing hormone in severely debilitated dogs with cancer.
Cachexia is a common manifestation of late stage malignancy and is characterized by anemia, anorexia, muscle wasting, loss of adipose tissue, and fatigue. Although cachexia is disabling and can diminish the life expectancy of cancer patients, there are still no effective therapies for this condition. We have examined the feasibility of using a myogenic plasmid to express growth hormone-releasing hormone (GHRH) in severely debilitated companion dogs with naturally occurring tumors. At a median of 16 days after intramuscular delivery of the plasmid, serum concentrations of insulin-like growth factor I (IGF-I), a measure of GHRH activity, were increased in 12 of 16 dogs (P < 0.01). These increases ranged from 21 to 120% (median, 49%) of the pretreatment values and were generally sustained or higher on the final evaluation. Anemia resolved posttreatment, as indicated by significant increases in mean red blood cell count, hematocrit, and hemoglobin concentrations, and there was also 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 GHRH gene transfer. We conclude that intramuscular injection of a GHRH-expressing plasmid is both safe and capable of stimulating the release of growth hormone and IGF-I in large animals. The observed anabolic responses to a single dose of this therapy might be beneficial in patients with cancer-associated anemia and cachexia.
Draghia-Akli
Ruxandra
R
ADViSYS, Inc. The Woodlands, Texas 77381, USA. ruxandradraghia@advisys.net
Hahn
Kevin A
KA
King
Glen K
GK
Cummings
Kathleen K
KK
Carpenter
Robert H
RH
D000818:Animals; D001835:Body Weight; D002100:Cachexia / Q000150:complications / Q000235:genetics* / Q000628:therapy* / Q000662:veterinary; D004283:Dog Diseases / Q000097:blood / Q000235:genetics* / Q000628:therapy*; D004285:Dogs; D015316:Genetic Therapy; D013007:Growth Hormone-Releasing Hormone / Q000235:genetics* / Q000627:therapeutic use*; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D009369:Neoplasms / Q000150:complications* / Q000235:genetics / Q000628:therapy / Q000662:veterinary; D010865:Pilot Projects; D010957:Plasmids / Q000235:genetics; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D014409:Tumor Necrosis Factor-alpha; D007334:Insulin-Like Growth Factor I; D013007:Growth Hormone-Releasing Hormone