Gene Doping

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Introduction Gene Doping
From This To
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This! Gene Doping! A New form of steroids for
athletes
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Gene Doping

• The use of Insulin Growth Factor I and
  Erythropoietin to Enhance Performance

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Overview

• Background Information
• Mechanisms of IGF-I (Insulin Growth Factor I) and
  EPO (Erythropoietin)
• Clinical Trials
• Potential Side Effects
• Take Home Message

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Overview

• Gene doping is the non-therapeutic use of genes,
  genetic elements and/or cells that have the
  capacity to enhance athletic performance
• Currently banned by WADA (World Anti-Doping
  Agency)
• Originated as a means to help individuals
  suffering from disease
• Muscular dystrophy, cancer, defective genes
• Injection into the cell, insertion of cells, or
  by using a virus as a carrier

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IGF-I Overview

• Use for treating muscle dystrophy
• Causes muscle hypertrophy and increased power
  production with degenerative muscle disease
• Attenuate affects of aging
• Maintain CSA and Type IIb fiber type
• Both thought to be major causes for
  hospitalization of older individuals

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EPO Overview

• EPO is a hormone produced by the liver and
  kidneys which contributes to the production of
  Red Blood Cells
• Endogenous injection of EPO can greatly help
  individuals that suffer from anemia

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Claims/Predictions For Use In Sport

• IGF-I has the potential to increase muscle mass
  in athlete creating a stronger, faster individual
• EPO has the potential for athletes to circulate
  more oxygen and increase cardiac output which can
  potentially increase time to exhaustion (TTE) and
  working level of VO2

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Mechanism of Action

• IGF-I
• Muscle is made up of long cylinders with multiple
  nuclei and cytoplasm consisting of myofibrils
• These myofibrils are made up of sarcomeres the
  contractile unit of the muscle
• Satellite cells manufacture proteins to
  build/repair these contractile units
• Satellite cells respond to IGF-I by undergoing a
  greater number of cell divisions
• This results in muscle hypertrophy which is one
  of the two mechanisms for increasing muscle
  strength and size

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Mechanism of Action

• EPO
• EPO is a glycoprotein produced mainly by the
  kidneys and liver
• Usually hypoxia lead to an increase in EPO
  production and receptors in the bone marrow
  enhance mitosis and differentiation of RBCs
• Recombinant EPO can be injected into a body in a
  non-state of hypoxia and thus can lead to the
  same RBC increases
• This can potentially increases oxygen carrying
  capacity

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Clinical Trials

• Barton-Davis et al (1998)
• IGF-I expression in mice found increased muscle
  size and nuclei density
• The interesting conclusion that they made was
  that the results would probably be used to
  improve athletic endeavors instead of disease
  treatment

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Clinical Trials

• Barton-Davis et al. (1998) EDL muscle in mice

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Clinical Trial

• Sweeney (2004)

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Clinical Trial
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Clinical Trials

• Coleman et al (1995)
• Transgenic overexpression of IGF-I in mice
  elicited pronounced hypertrophy in all classes of
  fibers
• Understand that IGF-I is a central growth factor
  that can result in significant improvements from
  growth and hypertrophy

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Clinical Trials

• Birkeland et al (2000)
• Randomized, placebo controlled study found that
  moderate doses of recombinant EPO over four weeks
  significantly increase VO2 max and ventilation
• Audran et al (1999)
• 26 days of EPO administration resulted in
  significantly increased VO2 max, endurance
  performance, physical work capacity
• Potential for creating a physiological advantage

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Potential Side Effects

• IGF-I
• The worry is that such an increase in muscle size
  will cause muscles to pull of the bone
• Scientists suggest that would be a problem in the
  elderly but not in athletes because athletes
  would have the time to adapt to meet the new
  demands
• EPO
• Increasing RBCs can increase viscosity causing
  the hearts contracting muscles to work harder and
  long term use can result in cardiac arrests
• 24 deaths have been reported between 1993-2003

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In Conclusion

• IGF-I
• There is no current testing methods of IGF-I
  supplementation
• However, due to the limited testing on human
  populations, the injection of IGF-I in athletes
  may have side effects that are currently unknown
• Injections requires medical facilities and
  practitioners

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In Conclusion

• EPO
• Currently the testing for EPO use is highly
  debatable and no precise testing protocol has
  been developed
• The use of EPO is not recommended because of the
  risk of increasing the bloods viscosity which
  can lead to cardiac arrest
• Injections requires medical facilities and
  practitioners

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Questions? Questions? Questions? Questions?