FOR RELEASE: May 29, 2001
Contact: Roger SegelkenOffice: 607-255-9736E-Mail: [email protected]
ITHACA, N.Y. -- The lives of cats suffering from nonregenerative anemia might be improved with the beginning of clinical trials of recombinant feline erythropoietin (rfEPO) developed by Cornell University veterinary researchers.
Nonregenerative anemia is the failure of bone marrow to produce red blood cells as a result of chronic renal disease, certain types of cancer and other chronic diseases.
Participation in the six-month clinical trials can be arranged by cat owners through their attending veterinarians, who will consult with researchers at the James A. Baker Institute for Animal Health in the College of Veterinary Medicine at Cornell.
The start of clinical trials using rfEPO with pet cats was announced May 25, 2001, at the American College of Veterinary Internal Medicine (ACVIM) Forum in Denver by James N. MacLeod, the Cornell associate professor of molecular genetics who developed recombinant feline EPO, as well as recombinant canine EPO, in collaboration with John F. Randolph, Cornell professor of medicine.
"EPO therapy isn't a cure for renal failure or cancer," emphasizes Randolph, a medicine internist specializing in endocrinology. "The value of recombinant EPO is that it can often be helpful in correcting the anemia associated with those conditions. Our goal is to improve the patient's strength, activity and appetite -- in other words, the animal's quality of life."
Erythropoietin (pronounced "eh-RITH--rho-POY-eh-tin") is the hormone normally produced by the kidneys of humans, cats and dogs, and other mammals to stimulate red blood cell production in bone marrow, explains MacLeod, a veterinarian with a Ph.D. in pathology and advanced training in genetics and endocrinology. "In chronic renal failure, the kidneys fail to produce sufficient erythropoietin, and in certain types of cancer, erythropoietin production and activity may be inhibited by cytokines (the substances that mediate inflammation) and chemotherapy drugs." Human erythropoietin (rhEPO) synthesized using recombinant DNA technology has been commercially available since 1989 and is widely used to support human red blood cell production, MacLeod notes. And rhEPO has been used in dogs and cats with erythropoietin-deficient anemia to stimulate an increase in red blood cell production.
"Unfortunately, in many treated companion animals, the effect is short-lived because of the development of antibodies against rhEPO," according to MacLeod. "Apparently there is enough variation in the molecular structure of erythropoietin among different animal species that the canine and feline immune systems can recognize human erythropoietin and mount an immune response against it."
Making matters worse, the antibodies produced by the cats and dogs being treated with recombinant human erythropoietin not only block the activity of rhEPO, but also might have the potential to "cross-recognize" whatever little of the cats' and dogs' own erythropoietin is still being produced. This can lead to the life-threatening bone marrow disorder called red blood cell aplasia.
Frustrated that a human hormone was only of limited help -- and even a detriment -- to the health of dogs and cats, MacLeod set about to develop synthetic forms of EPO that the animals' immune systems could accommodate. In 1993, the gene for canine EPO was isolated in his laboratory, and the feline gene was isolated by Baker Institute scientists Robin Bell and Richard Goodman. MacLeod and his Cornell colleagues proved that the dog and cat genes could be expressed to make a highly purified form of canine EPO and feline EPO, respectively, and that quantities of recombinant EPO could be produced in cultures by genetically engineered cell lines.
Randolph and MacLeod began tests of canine EPO in a laboratory setting in 1997, and they are now part way through a three-year, multicenter trial with collaborators at Cornell and other veterinary schools, as well as at major veterinary clinics across the country. Their study is evaluating the effectiveness of canine EPO therapy in three types of patients: dogs with chronic renal failure, dogs with lymphosarcoma and dogs whose red blood cell counts crashed after treatment with recombinant human EPO.
Following the same pattern, recombinant feline EPO was first tested at Cornell in 1999, and now, with approval of the FDA, clinical trials can begin with the same nonregenerative anemia conditions. Patents for these technologies have been secured through the Cornell Research Foundation. Chronic renal failure is a progressive and irreversible deterioration in kidney function frequently encountered in middle-aged and older cats. Lymphosarcoma, or cancer of lymphoid tissue, is one of the most common feline cancers. Special diets and phosphate binders are prescribed by veterinarians as a medical management strategy for renal failure to prolong cats'
lives for months or years -- unless anemia becomes a problem. Similarly, chemotherapy for lymphosarcoma can result in remission and allow survival for six to 12 months -- without the complications of anemia.
Cats under consideration for the rfEPO trials must be at least 1 year old and meet other medical criteria. After initial tests and admission to the clinical trial, the rfEPO is injected under a cat's skin -- initially, three times a week and then tapered, depending on response. Throughout the trial, blood tests will determine whether the feline EPO treatment is boosting production of red blood cells. Other diagnostic and therapeutic costs are the responsibility of the cat owners, although the rfEPO and blood tests during the clinical trial are free of charge. Cat owners seeking admission to the rfEPO trials must do so through their local veterinarians.
The studies of canine and feline recombinant erythropoietin have been supported by the Baker Institute for Animal Health, Collie Club of America Foundation, Morris Animal Foundation, Pfizer Animal Health, the Alumni Grants Fund of Cornell University, the Cornell Feline Health Center, the Winn Feline Foundation and by gifts from private individuals.
Related World Wide Web sites: The following sites provide additional information on this news release. Some might not be part of the Cornell University community, and Cornell has no control over their content or availability.
o James A. Baker Institute for Animal Health: http://bakerinstitute.vet.cornell.edu/
o Cornell College of Veterinary Medicine: http://www.vet.cornell.edu/
o Cornell University Hospital for Animals: http://www.vet.cornell.edu/hospital/
-30-
RSS