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Expression, bioactivity, and clinical assessment of recombinant feline erythropoietin

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  • 1 Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.
  • | 2 Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.
  • | 3 Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.
  • | 4 Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.
  • | 5 Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.

Abstract

Objective—To determine the activity of recombinant feline erythropoietin (rfEPO) in murine bioassays and evaluate its efficacy and safety in cats with erythropoietin-dependent nonregenerative anemia.

Animals—26 cats (group 1, 19 cats with anemia attributed to chronic kidney disease [CKD]; group 2, 7 cats with CKD and recombinant human erythropoietin [rhEPO]-induced red cell aplasia [RCA]).

Procedure—The rfEPO was synthesized by use of Chinese hamster ovary (CHO) cells transfected with feline erythropoietin complementary DNA. Preclinical assessments of rfEPO included an erythroid cell proliferation assay and measurements of reticulocytosis in Balb/C mice. Clinical assessments of cats included hematologic, biochemical, and clinical examinations during 12 (group 1) or 6 (group 2) months of rfEPO treatment.

Results—Biological activity of rfEPO was broadly equivalent to rhEPO in preclinical murine bioassays. Median Hct and absolute reticulocyte count in cats increased significantly during the first 3 weeks of rfEPO treatment, and median Hct generally could be maintained within a target range of 30% to 40% with periodic adjustments of rfEPO doses. Unexpectedly, 5 cats in group 1 and 3 cats in group 2 that initially responded to rfEPO treatment again developed anemia that was refractory to additional rfEPO treatments, even at higher doses.

Conclusions and Clinical Relevance—Treatment with rfEPO can reestablish active erythropoiesis in most cats with CKD, even those with anemia attributable to rhEPO-induced RCA. Unfortunately, development of RCA during treatment with CHO cell-derived recombinant erythropoietin proteins was not eliminated as a serious safety concern, even for this feline-specific preparation. (Am J Vet Res 2004;65:1355–1366)

Abstract

Objective—To determine the activity of recombinant feline erythropoietin (rfEPO) in murine bioassays and evaluate its efficacy and safety in cats with erythropoietin-dependent nonregenerative anemia.

Animals—26 cats (group 1, 19 cats with anemia attributed to chronic kidney disease [CKD]; group 2, 7 cats with CKD and recombinant human erythropoietin [rhEPO]-induced red cell aplasia [RCA]).

Procedure—The rfEPO was synthesized by use of Chinese hamster ovary (CHO) cells transfected with feline erythropoietin complementary DNA. Preclinical assessments of rfEPO included an erythroid cell proliferation assay and measurements of reticulocytosis in Balb/C mice. Clinical assessments of cats included hematologic, biochemical, and clinical examinations during 12 (group 1) or 6 (group 2) months of rfEPO treatment.

Results—Biological activity of rfEPO was broadly equivalent to rhEPO in preclinical murine bioassays. Median Hct and absolute reticulocyte count in cats increased significantly during the first 3 weeks of rfEPO treatment, and median Hct generally could be maintained within a target range of 30% to 40% with periodic adjustments of rfEPO doses. Unexpectedly, 5 cats in group 1 and 3 cats in group 2 that initially responded to rfEPO treatment again developed anemia that was refractory to additional rfEPO treatments, even at higher doses.

Conclusions and Clinical Relevance—Treatment with rfEPO can reestablish active erythropoiesis in most cats with CKD, even those with anemia attributable to rhEPO-induced RCA. Unfortunately, development of RCA during treatment with CHO cell-derived recombinant erythropoietin proteins was not eliminated as a serious safety concern, even for this feline-specific preparation. (Am J Vet Res 2004;65:1355–1366)