Transcript GENE DOPING IN SPORTS - Καλώς ήρθατε στον

GENE THERAPY IN SPORTS
Mechanisms & Bioethics
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
Why “somatic”

Somatic cells do not contribute to the germ
line
 Germ cells alterations will be transmitted to
progeny
Gene transfer manner

Ex vivo: cells explanted-cultured-gene transfertransformed-reinfused
 In vivo local: intramuscular, intrajoint etc,
localised diseases indication,limits toxicity of gene
transfer & contamination of germ line
 In vivo systemic:intravascular,intraperitoneal- no
specific trapping, germ line ?
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
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)
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)
Gene therapies that can be
abused in sports

Systemic proteins:EPO,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 growth:FGF-1,2,4 or 5,
vascular endothelial growth factor
….

Pain relief: endorphins, enkefalins,
analgesic peptides
 Neurological: hormone/growth factors,
pituitary/hypothalamic cognition/memory
enhancers,mood altering
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)
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
Ways to detect Gene therapy

Antibodies to viral proteins- viral DNA
 Quantitative gene chip analysis before and
after
 Over/under expressed gene’s product
New Scientist journal, “gene cheats” 2000
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
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
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)
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
