Some veterinarians use a newer form of the human hormone erythropoeitin (EPO) called darbepoeitin to treat anemia associated with rental failure. EPO, produced in the kidney, signals the bone marrow to create red blood cells. Treatment of cats with this latest version of EPO has shown greater promise than the use of human EPO used in the past but remains problematic.
In some cases, treated cats form antibodies against darbepoeitin. This is because the protein structure of human EPO differs from the feline form of the protein. Antibodies directed against darbepoietin can even cross against the cat’s own EPO, resulting in an autoimmune response that can be fatal.
At the UC Davis School of Veterinary Medicine, Brian Murphy, DVM, Ph.D., and colleagues want to use the cat’s own EPO gene product to avoid the potential for autoimmune rejection.
They started by isolating feline kidney tissue from a cat cadaver and cloning feline EPO from it. That was the relatively easy part, Dr. Murphy says. “The trick is to try to get the feline gene introduced into cat cells and have stable long-term expression. To do so, we plan to use a modified virus, a gene therapy vector. The gene therapy vector ‘infects’ the feline cells temporarily, introducing the feline EPO into the cat’s own DNA.” The eventual goal: re-infusing an anemic cat with his own genetically modified cells, stably producing feline EPO.
As with all gene therapy, safety mechanisms are vital. “There’s a concern if we introduce the gene into the wrong chromosomal location, it could have a negative result, perhaps something like leukemia,” Dr. Murphy says. “With modern gene therapy vectors, there’s little evidence that this is happening, but we have created a ‘kill switch’ within our vector. If we determine that the cells are autonomously replicating and creating something that looks like a tumor, we can treat the cat with a drug to destroy all of the genetically modified cells.”
So far, Dr. Murphy has tested the cells only in the laboratory and has demonstrated the production of functional feline EPO in cat cells.
Owners who hear about his studies ask him to try the gene therapy strategy on their ailing cats. “I tell these people that at this stage of the project, we can’t ethically do that. I don’t want to take an animal that is debilitated because of kidney disease and then introduce something that might do harm and further shorten the life of the cat,” he says.
Dr. Murphy’s initial studies have been supported by grants from the Winn Feline Foundation and the Morris Animal Foundation. “This treatment strategy has a really good chance for eventual success,” he says. “It’s just a question of time before the technical problems are resolved.”