342. Human Erythropoietin Gene Therapy for Patients with Chronic Renal Failure

Top of pageAbstract Background: Gene therapy holds a major promise. However, until now, this promise was fulfilled only in few cases, in rare genetic diseases. One very common clinical condition is anemia. Patients with anemia of chronic renal failure are treated with Erythropoietin. The objective of this study was to develop a therapeutic platform for serum secreted proteins like erythropoietin. Method: We developed a tissue protein factory based on dermal cores (Biopump) harvested and implanted autologously. In this study, an adenovector was designed to express the human Erythropoietin under the control of the CMV promoter. This vector transduced the harvested dermal cores ex vivo. The transduced cores were implanted and Erythropoietin and reticulocyte counts were measured. Results: Dermal cores were harvested from 13 patients with chronic renal failure, and implantation was performed in 10. There were no significant drug related side- effects to this procedure. Erythropoietin serum levels increased significantly to therapeutic levels from day 1 post implantation reaching a peak during the first week of follow-up. The expression period was transient for up to 14 days. The rise of Erythropoietin was followed by a transient significant increase in reticulocyte counts. The decrease of Erythropoietin expression coincided with a significant dermal infiltrate of CD8 cytotoxic T cells. Anti Erythropoietin antibodies were not detected until day 90 following implantation. Conclusion: Implantation of dermal cores ex vivo transduced with human genes could eventually be used in the clinical setting to express therapeutic serum proteins. However, non-immunogenic delivery system should be tested as gene vehicles. The company Medgenics Inc., Biogenics Ltd had supported this study. However, painfully we must say that the company went out of business recently, and the authors of this abstract have no more financial connections to it.