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Repoxygen

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Repoxygen is the tradename for a type of gene therapy that induces controlled release of erythropoietin (EPO) in response to low oxygen concentration. It has been developed by Oxford Biomedica to treat anaemia. It has been developed in mice, is still in preclinical development and has not been extensively tested in humans.

It is constructed as a viral gene delivery vector carrying the human EPO gene under the control of a so-called "hypoxia control element" (“HRE”). The HRE is claimed to sense low oxygen concentrations and to switch a gene on in response. Repoxygen is designed to be delivered by injection into muscle and therefore to induce syntheses of EPO in the muscle tissue. Normally, EPO is synthesized in the liver and kidneys. It leads to increased production of red blood cells.

Use of recombinate EPO DNA in mice has shown protective effects for epithelial cells and is being investigated as a prophylatic treatment for lung tissue injury.

Excess EPO, the signalling hormone for more red blood cell production (increased erythrocytes), can lead to erythrocytosis—a condition of too many red blood cells. Erythrocytosis makes the blood thicker and more viscous, making pooling and clotting more likely, and represents an increased stress on the heart (due to the thicker blood). Erythrocytosis is potentially fatal, especially in endurance athletes who are frequently dehydrated during long events.

Doping

Athletes could consider using Repoxygen as a means of increasing their number of red blood cells. Due to its alleged self-regulating properties it may be impossible to detect Repoxygen. Repoxygen is prohibited both in and out of competition under the World Anti-Doping Code 2006 Prohibited List.

Thomas Springstein, a former track coach for the German national team, attempted to order repoxygen for the purpose of boosting the performance of his athletes. The ability of repoxygen to boost red blood cell count in the body is invaluable to endurance athletes, which is a part of the reason for the perceived interest in the substance.[1] Consequently, the World Anti-Doping Agency is researching detection methods for substances such as repoxygen.[2]

Repoxygen's delivery vector has triggered immune response in several cases and resulted in at least one confirmed death directly related to the body's immune response to the viral protein delivery vehicle.

EPO is un-regulated in anoxic environments such as high-altitude climbing; Repoxygen and other gene therapies may find "legal doping" applications in such sports. High-altitude mountain climbing (i.e. attempting to summit Death Zone mountain peaks without supplemental oxygen), or extreme deep diving (requiring ones to hold their breath for several minutes while diving 100+ feet) are two examples.

References

  1. ^ Reynolds, G.. (June 3, 2007). Outlaw DNA. In New York Times. Retrieved April 11, 2012
  2. ^ World Anti Doping Agency. (October 2009). Gene Doping. In World Anti-Doping Agency. Retrieved April 11, 2012, from http://www.wada-ama.org/en/Science-Medicine/Science-topics/Gene-Doping/.

Additional reading

  • Yoshimi M, Maeyama T, Yamada M, Hamada N, Fukumoto J, Kawaguchi T, Kuwano K, & Nakanishi Y. (2008). Recombinant human erythropoietin reduces epithelial cell apoptosis and attenuates bleomycin-induced pneumonitis in mice. Respirology 13(5). 639-645.
  • Percy MJ. (2008). Familial erythrocytosis arising from a gain-of-function mutation in the HIF2A gene of the oxygen sensing pathway. Ulster Medical Journal 77(2). 86-88.
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