Erythropoietin Abuse and Erythropoietin Gene Doping

Abstract

The administration of recombinant human erythropoietin (rhEPO) increases the maximum oxygen consumption capacity, and is therefore abused as a doping method in endurance sports. The detection of erythropoietin (EPO) abuse is based on direct pharmacological and indirect haematological approaches, both of which have several limitations. In addition, current detection methods cannot cope with the emerging doping strategies of EPO mimicry, analogues and gene doping, and thus novel detection strategies are urgently needed. Direct detection methods for EPO misuse can be either pharmacological approaches that identify exogenous substances based on their physicochemical properties, or molecular methods that recognise EPO transgenes or gene transfer vectors. Since direct detection with molecular methods requires invasive procedures, it is not appropriate for routine screening of large numbers of athletes. In contrast, novel indirect methods based on haematological and/or molecular profiling could be better suited as screening tools, and athletes who are suspect of doping would then be submitted to direct pharmacological and molecular tests. This article reviews the current state of the EPO doping field, discusses available detection methods and their shortcomings, outlines emerging pharmaceutical and genetic technologies in EPO misuse, and proposes potential directions for the development of novel detection strategies.

Raves and risks for erythropoietin

“…Irrespective of the problems associated with EPO abuse and gene doping [74], EPO has been correlated with the alteration of red cell membrane properties leading to a cognitive decrement in rodent animal models [2,3]. In addition, development of potentially detrimental side-effects during EPO therapy, such as for cerebral ischemia with increased metabolic rate and blood viscosity [75], could severely limit or halt the use of EPO for neurovascular diseases.…”

The use of genes for performance enhancement: doping or therapy?

“…Additionally, rhuEPO is used to minimize allogeneic blood transfusions after major surgical procedures. Notoriously, rhuEPO has also been illicitly used for enhancement of sport performance (28).…”

Terapia gênica, doping genético e esporte: fundamentação e implicações para o futuro

“…Erithropoetin is a protein produced in the kidneys whose main effect is the stimulus of the hematopoese (25) . Therefore, the additional copy of the gene which codifies the erithropoetin results in the increase of the production of red blood cells; consequently, the capacity of O 2 transportation to the tissues is increased.…”

“…Research with rats and macaques successfully transferred an additional copy of the erithropoetin gene (12,(25)(26) , suggesting that this kind of doping is already possible. Nevertheless, it is not very probable that the super-expression of erithropoetin had important harmful effects in healthy individuals, once a remarkable increase of the monkeys' hematocrit has been observed (from 40% to approximately 80%) (12) .…”

“…Nevertheless, this kind of treatment may carry a potential risk of misuse by athletes who search for physical performance improvement, as occurs in high level sport. The misuse of this therapy is called gene doping and has been issue of a scientific-academic debate whose importance has been growing in sports medicine and sports sciences (21)(22)(23)(24)(25)(26)(27) .…”