Gene Therapy enhancement of IGF1 production triples endurance in mice

ATHLETES trying to cheat by loading their bodies with genes that make muscles bigger and more efficient could be caught if forced to supply muscle biopsies, but not through the analysis of urine or blood samples.
 
So says Mauro Giacca of the International Centre for Genetic Engineering and Biotechnology in Trieste, Italy, who was asked by the World Anti-Doping Agency to look into how to screen for gene doping.
 
To do so, Giacca’s team created mice loaded with extra copies of the muscle-boosting gene IGF-1, which codes for the protein insulin-like growth factor 1, by injecting its limbs with a virus that implants IGF-1 into muscle cells. They then tested the animals’ endurance by recording how long they could swim before exhaustion. The doped mice swam for three times as long as mice that received the virus but not IGF-1.
 
Autopsies showed that the extra IGF-1 triggered the production of 10 times more protein than normal in the muscles. Giacca also saw activity soar in genes controlling energy production, contraction of muscles and respiration. Also detectable in the muscle were traces of the virus used to deliver the genes. However, the gene, protein and virus were undetectable in blood or urine from the mice (Human Gene Therapy, DOI: 10.1089/hum.2011.157).
 
Giacca doubts it is possible to achieve such results through exercise alone. So "from a muscle biopsy, it would be possible to distinguish a well-trained athlete from one who’d been gene-doping for a month", he says.
 
"It may be possible to look for unusual changes in gene profiles, but if this relies on muscle biopsies it won’t happen," says Lee Sweeney, of the University of Pennsylvania in Philadelphia, who created the world’s first IGF-1 "supermice" in 2004.
 
Giacca doubts whether athletes will attempt gene doping in the run-up to this year’s Olympic games, because it is technically challenging, but he says they may in the future – most likely through an illegal government programme.
 
He is now working on a study to identify, in blood and urine, raised levels of micro RNA related to gene doping.