Repoxygen
Definition
Repoxygen is a product developed by the British company Oxford BioMedica for the treatment of anemia. It is a gene therapy procedure that, however, has so far only been tested in animal experiments on mice. The company published relevant information on its website as early as 2002.
The procedure was not further developed for use in humans. One reason for this was that the company saw no market potential compared to existing erythropoietin (EPO) products (injectable preparations based on genetically engineered EPO).
Significance as a Doping Agent
The use of Repoxygen in sports can be considered gene doping and is prohibited as a doping method. It does not matter whether the product is approved for medical use in humans or not.
For doping purposes, the preparation would be of little use based on the described mechanism of action, since the EPO gene is not activated under normal blood values and corresponding oxygen saturation, and thus EPO production beyond the normal physiological level—as desired in a doping measure—is not expected to occur.
Effects
Oxford BioMedica has developed a viral gene delivery system in the form of a vector carrying the human EPO gene. This vector delivers the genetic information on how the body synthesizes EPO into the nucleus of muscle cells. The muscle cells then produce increased amounts of EPO, which stimulates the synthesis of erythrocytes (red blood cells) in the bone marrow. An increase in erythrocytes improves oxygen supply and can normalize an anemic condition.
However, if EPO production is not controlled, an overproduction of erythrocytes can increase blood viscosity and lead to a life-threatening condition caused by thrombosis. Therefore, to control EPO production, an oxygen-sensitive factor was simultaneously developed that regulates the activity of the EPO gene. This factor responds to a lack of oxygen in the blood and consequently activates the EPO gene. Once physiologically normal red blood cell levels and oxygen levels in the blood are achieved, the oxygen-sensitive factor causes the EPO gene to be switched off.
Detection
Can a possible unauthorized use of Repoxygen be detected? Studies by Francoise Lasne (Lasne et al. 2004) in monkeys show that gene doping with the human EPO gene in muscle cells produces EPO variants that differ from physiological EPO—which is normally produced by kidney cells—based on their carbohydrate content.
These different EPO variants can be detected through urine analysis. When Repoxygen is used, the target cells are also muscle cells, and altered EPO patterns compared to the EPO normally produced in the kidneys are to be expected.