Have You Heard? Treating complications of chronic renal failure with gene therapy (script)
Chronic renal failure is common in geriatric cats and dogs, and deteriorating kidney function is compounded by a catabolic state responsible for many of the complications of this disease, such as anemia and weight loss.
Chronic renal failure is common in geriatric cats and dogs, and deteriorating kidney function is compounded by a catabolic state responsible for many of the complications of this disease, such as anemia and weight loss. The treatment options for veterinary patients are limited and frequently consist of nutritional management and fluid therapy. The options in people with renal failure are equally limited and generally involve long-term dialysis or kidney transplantation.
Chronic renal failure affects growth hormone-releasing hormone as well as growth hormone and its mediator, insulin-like growth factor 1. In human medicine, patients treated with recombinant growth hormone show significant improvements in immune function, anemia, wasting, and other common complications of chronic renal failure. However, the daily injection protocol is not practical.
A recent study published in BMC Biotechnology looked at treating chronic renal failure and its complications in cats and dogs with growth hormone-releasing hormone plasmid-based therapy. The animals in the study received a single plasmid injection intramuscularly followed by electroporation. Electroporation, an externally applied electrical current, increases cell permeability, allowing the introduction of substances directly into cells. This technique has made one-time low-dose gene therapy possible.
Thirty dogs and 30 cats with chronic renal failure based on the results of a physical examination, serum chemistry profile, and urinalysis were accepted into the study. Before gene therapy, all of the patients were treated with fluids and specialized diets. Study participants were anesthetized and given a single species-specific plasmid injection into the semitendinosus muscle followed by three electroporation pulses before anesthetic recovery and being returned to their owners. The animals were reevaluated 20, 40, and 75 days after treatment. Additionally, 12 dogs and 15 cats with chronic renal failture were selected as control animals and received fluids, nutritional management, and electroporation without a plasmid injection.
The results of the study revealed no adverse effects noted by the animals' owners or veterinarians. Treatment with growth hormone-releasing hormone led to increased survival times. Treated animals had increased body weight, improved hematologic parameters, increased serum albumin and total protein concentrations, and stable serum creatinine and blood urea nitrogen concentrations. Overall kidney function was maintained in the treated animals, while the control group continued to deteriorate. Quality of life parameters such as activity and exercise level, appetite, and mentation significantly improved in the treated dogs and cats.
While gene therapy with electroporation is not widely available in the veterinary field, this study suggests that possibilities exist for its use in treating severe metabolic conditions and chronic diseases. Previous reports show success with this technique for improving the conditions for dogs with cancer and treating laminitis in horses. Further research may lead to additional uses and eventually provide more options for veterinarians and physicians to improve quality of life for chronically ill patients.
Source: Brown PA, Bodles-Brakhop AM, Pope MA, et al. Gene therapy by electroporation for the treatment of chronic renal failure in companion animals. BMC Biotechnol 2009;9:4.