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Anemia is a condition whereby there are too few red blood
cells in the circulation. Whenever I encounter a pet with anemia, I
embark on a mission to discover the cause of the anemia, so as to
formulate a treatment plan.
Anemias can be broadly divided into two
categories: regenerative and non-regenerative. A regenerative anemia
is one in which the bone marrow recognizes that the body is deficient in
red blood cells. The bone marrow then actively tries to replenish the
blood stream with red blood cells by cranking them out as best as they
can. Regenerative anemias tend to be caused by blood loss, or as a
result of red blood cell destruction by the immune system.
Non-regenerative anemias, on the other hand, are those in which the bone
marrow does not or cannot respond to the anemia. Although there are
several potential causes for non-regenerative anemia in companion
animals, by far the most common cause is chronic renal failure (CRF).
As a veterinarian specializing in cats, whenever I encounter a cat with
non-regenerative anemia, the vast majority of the cases are indeed a
result of kidney failure, with most of the remaining cases due to
infection with the feline leukemia virus (FeLV). These two disorders,
by the way, are the number 1 (FeLV) and number 2 (CRF) causes of death
in pet cats.
The kidneys produce a hormone,
erythropoietin, that instructs the bone marrow to produce red blood
cells. When a cat becomes anemic, the kidneys produce and release more
erythropoietin so that the bone marrow can produce more red blood
cells. With chronic renal failure, the damaged kidneys cannot produce
enough erythropoietin, and cats become anemic. Red blood cells carry
oxygen to the muscles and other organs, and without enough red blood
cells, cats become weak, lethargic, and often show decreased appetite.
In 1989, using genetically engineered cell
lines and recombinant DNA technology, researchers synthesized human
recombinant erythropoietin (rhEPO) for use in human patients with
non-regenerative anemia. This product has been used successfully in
dogs and cats with erythropoietin-deficient anemia.
Unfortunately, the immune system of some cats recognizes
the genetically engineered rhEPO as being of human origin, and they
mount an immune response against it by producing antibodies that attack
and neutralize it. Making matters worse, these antibodies can
“cross-recognize” whatever small amount of the cats’ own erythropoietin
is still being produced. The red blood cell count rapidly plunges to
life-threatening levels for which there is no treatment other than a
blood transfusion. This happens in 25 to 33% of cats receiving rhEPO.
One way around this problem would be to
administer genetically engineered erythropoietin of feline origin,
however, the market for such a product is small compared to the human
market, and major pharmaceutical companies are reluctant to invest the
huge sums of money needed to develop and market a new drug with little
chance of recouping their investment. Dr. James McLeod, a veterinary
pathologist and associate professor of molecular genetics at Cornell
University, devoted himself to this problem soon after rhEPO was
developed, and in 1993, the gene for canine EPO was isolated in his
laboratory. Collaborating with Dr. John Randolph, these two scientists
began testing canine EPO in 1997. When Robin Bell and Richard Goodman
of the James A. Baker Institute for Animal Health at the College of
Veterinary Medicine at Cornell isolated the feline EPO gene, Dr. MacLeod
and his Cornell colleagues proved that the cat gene could be manipulated
to make a highly purified form of feline EPO (rfEPO) using
genetically engineered cell lines. Initial testing took place in 1999.
Working with Cornell professor of Medicine John F. Randolph, Dr. MacLeod
has been conducting, with approval from the FDA, clinical trials of
rfEPO on pet cats with non-regenerative anemia. According to an e-mail
I received from Dr. Macleod, the clinical trials have been completed.
The raw data is being evaluated and a full analysis of the hematological
data is still pending. A manuscript detailing the clinical response to
the drug will be submitted for publication later this year.
Chronic renal failure is a progressive
disease for which there is no cure. Once diagnosed, veterinarians try
to do what they can to slow the progression of the disease (see the
April and May 2003 Feline Frontiers columns) and prescribe medications
and other therapies to make the affected cat as comfortable as
possible. By treating the anemia that accompanies chronic renal
failure, we may be able to significantly affect cats’ quality of life by
improving their strength, activity, and appetite. Whether rfEPO becomes
available for general use, however, will depend on whether a company
will be willing to invest the time and money necessary to obtain
approval from the FDA. Dr. MacLeod says he’s hopeful that this will
happen eventually, “but at present is not a process that is underway to
my knowledge”. Until then, unfortunately, rfEPO is unavailable for
privately-owned cats. (I urge my readers to refrain from contacting
Cornell University about this; without FDA approval, they are legally
prohibited from dispensing the drug). I feel confident that one day
in the near future, species-specific erythropoietin preparations will be
available for both cats and dogs, giving us one more piece of ammunition
in our continuing battle against this insidious disease.
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