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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, theoretically, would be to administer genetically
engineered erythropoietin of feline origin. Sadly, 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. Nevertheless, 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. 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.
Unfortunately, the results using recombinant feline erythropoietin have
been discouraging. A study published in 2004 in which 19 cats with
nonregenerative anemia due to erythropoietin deficiency were given the
genetically engineered feline erythropoietin. The biological activity
of the drug was similar to the human formulation, and the red blood cell
count increased nicely during the first few weeks of therapy.
Unexpectedly, however, 5 of the cats developed sudden severe anemia that
did not respond to additional amounts of feline erythropoietin. For
some unknown reason, something in the feline erythropoietin formulation
triggered antibody production. Species-specific EPO rarely induces
antibodies in people (less than 1 in 10,000 cases), and canine EPO
doesn’t induce antibodies when given to dogs, but for unknown reasons,
feline EPO does induce antibodies in cats, at a rate that is almost
similar to that seen when using human EPO on cats. Hopefully, the
trigger for antibody production will be revealed so that future
preparations of recombinant feline EPO can be developed that do not
stimulate an immune response, giving us another tool in our
armamentarium for treating anemia, especially in cats with chronic renal
failure.
Updated 2/9/06 |
