GENE THERAPY IN SPORTS Mechanisms Bioethics Gene Therapy

GENE THERAPY IN SPORTS Mechanisms & Bioethics

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

Why “somatic” l Somatic cells do not contribute to the germ line l Germ cells alterations will be transmitted to progeny

Gene transfer manner Ex vivo: cells explanted-cultured-gene transfertransformed-reinfused l In vivo local: intramuscular, intrajoint etc, localised diseases indication, limits toxicity of gene transfer & contamination of germ line l In vivo systemic: intravascular, intraperitoneal- no specific trapping, germ line ? l

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

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

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

Gene therapies that can be abused in sports l Systemic proteins: EPO, growth hormone l Wound or injury healing: bone repair factors, PDGF, KGF l Increase muscle mass: angiogenic factors to skeletal and heart muscle, IGF 1 l Blood vessel growth: FGF-1, 2, 4 or 5, vascular endothelial growth factor

…. l Pain relief: endorphins, enkefalins, analgesic peptides l Neurological: hormone/growth factors, pituitary/hypothalamic cognition/memory enhancers, mood altering

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

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

Ways to detect Gene therapy l Antibodies to viral proteins- viral DNA l Quantitative gene chip analysis before and after l Over/under expressed gene’s product New Scientist journal, “gene cheats” 2000

Ethics l 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 l The Entertainment View extraordinary performance- genetic modification desirable l The Techno-Centered View GM simply a sophisticated technological character –eventualy can make the game fair l

Is “natural” mutation an unfair advantage? l Eero Mantyranta two golden medals in cross -county skiing in 1964 Winter Olympics l Mutation in gene that produces the receptor for EPO l O 2 normal- EPO receptor should shut down epo production but not in Mantyranta (mutation turned off this crucial feedback)

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