GENE THERAPY IN SPORTS

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GENE THERAPY IN SPORTS

• Mechanisms Bioethics

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Gene Therapy

• Gene transfer in somatic cells to heal or treat
  disorders
• Strategy that can be applied to
• chronic,acute or preventive treatments
• hereditary or acquired diseases

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Why somatic

• Somatic cells do not contribute to the germ line
• Germ cells alterations will be transmitted to
  progeny

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Gene transfer manner

• Ex vivo cells explanted-cultured-gene
  transfer-transformed-reinfused
• In vivo local intramuscular, intrajoint etc,
  localised diseases indication,limits toxicity of
  gene transfer contamination of germ line
• In vivo systemicintravascular,intraperitoneal-
  no specific trapping, germ line ?

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Non Viral Viral transfer vehicles

• Non viral cell membrane not strong barrier but
  lack of transport into cell nucleous
• Viral get internalised,remain protected from
  cytoplasmic enzymes,genetic load into nucleous

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Non viral

• Naked DNA complex formulations into liposomal
  particles
• Oligonucleotides small gene fragments, swamp
  pathological factors,gene repair inducers, short
  persistance (good candidates in transient
  treatments in doping arena)

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Viral

• Adenoviruses favourite system,relatively
  large,can carry big gene, valnerable to attack
  from immune system
• Adeno-associated viruses(AAVs)smaller, less
  valnerable,transfer small-size genes
• Retroviruses risk of insertional mutagenesis,
  can affect non dividing cells (ex brain)

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Gene therapies that can be abused in sports

• Systemic proteinsEPO,growth hormone
• Wound or injury healing bone repair
  factors,PDGF, KGF
• Increase muscle mass angiogenic factors to
  skeletal and heart muscle,IGF 1
• Blood vessel growthFGF-1,2,4 or 5, vascular
  endothelial growth factor

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.

• Pain relief endorphins, enkefalins, analgesic
  peptides
• Neurological hormone/growth factors,
  pituitary/hypothalamic cognition/memory
  enhancers,mood altering

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Feared potential side effects

• Viral vectors can stimulate immune system (acute
  toxic shock)
• Repeated dosing leads to antibodies against virus
  which is stopped before gene delivery (ex. Muscle
  damage through exercise)
• Over expression (monkeys with too much EPO need
  bleeding)- new nucleotides insertion to switch
  on/off the gene(Lin et al)

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Side effects

• Expressed gene product can be recognised as non
  self in individuals(factor VII in haemophiliac
  dogs)
• Random integration in the genome
  (oligonucleotides) is genotoxic- increases risk
  of cancer
• Germ cell contamination

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Ways to detect Gene therapy

• Antibodies to viral proteins- viral DNA
• Quantitative gene chip analysis before and after
• Over/under expressed genes product
• New Scientist journal, gene cheats 2000

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Ethics

• Accumulation of values and principles that
  address questions of what is good or bad in human
  affairs
• www.austlii.edu.au/au/other/alrc
• protection of human genetic information

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Bioethics

• The Romantic View
• integrity of sport threatened by technology
• The Entertainment View
• extraordinary performance- genetic
  modification desirable
• The Techno-Centered View
• GM simply a sophisticated technological
  character eventualy can make the game fair

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Is natural mutation an unfair advantage?

• Eero Mantyranta two golden medals in cross-county
  skiing in 1964 Winter Olympics
• Mutation in gene that produces the receptor for
  EPO
• O2 normal- EPO receptor should shut down epo
  production but not in Mantyranta (mutation turned
  off this crucial feedback)

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questions

• Elite genes
• Pre selection of athletes according to geno type
• Bioethics about children and even embryos
• DNA data of the whole population with severe even
  political implications

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