Mighty mice offer hope for sick

By SIMON COLLINS


World-leading New Zealand research on muscular "mighty mice" may point the way to restoring wasted muscles in people suffering from cancer, diabetes, muscular dystrophy and HIV.

A husband-and-wife team at AgResearch's Ruakura Research Centre, Dr Ravi Kambadur and Dr Mridula Sharma, found a genetic mutation in double-muscled Belgian Blue cattle in 1997 which knocks out a protein that normally stops muscles growing too big.

They have now developed a "lookalike" molecule which blocks the muscle-limiting protein in mice and may cure muscle-wasting conditions in humans.

The molecule has been patented and licensed to the sheep-research company Ovita. New Zealand taxpayers and the country's 25,000 sheep and beef farmers stand to share the profits if the molecule works in humans, through Ovita's three equal shareholders - state-owned AgResearch, Wool Equities and Meat and Wool NZ.

Among the first to benefit could be the 4000 New Zealanders with muscular dystrophy, a genetically inherited condition which causes the muscles to gradually waste away until most patients die.

Ultimately, Dr Kambadur believes it could help millions of people around the world whose muscles wither in response to cancer, diabetes, HIV/Aids or just age.

"One-third of cancer patients don't die of the cancer tumour, they die of muscle-wasting," he said.

"Diabetes affects the muscles because muscles burn sugar. The muscles develop resistance to insulin - they forget how to use insulin."

Muscles can make up to three-quarters of a fit person's body. American body-building websites are already speculating that athletes will soon latch on to the new technology to achieve "super-human" feats.

The protein which normally limits muscle growth is myostatin (myo=muscle, statin=stop). Abnormally high levels of myostatin have been found in HIV patients and in elderly people.

At the other extreme, a 4-year-old German boy four months ago became the first human being with no myostatin in his body to be reported in the medical literature.

At 4, the boy can hold 3kg weights. His mother, a former professional athlete, inherited the same genetic mutation from one of her parents but the boy has inherited it from both his parents.

Indian-born Dr Kambadur and Dr Sharma, who came to New Zealand in 1996, are in a race against several rival teams to find the best way to use the new knowledge.

An American group has genetically modified mice by knocking out the gene that controls myostatin, producing rodents with muscles twice as big as usual.

The Ruakura team bought some of the mice and originally planned to knock out the same gene in sheep.

They gained a controversial permit in 2000 to create a flock of up to 100 genetically modified (GM) sheep, expecting that the lean, fat-free meat of sheep without myostatin would also be more tender.

But the plan was vetoed by Ovita when the new company took over the research funding in 2002. Ovita chief executive Damian Camp said yesterday the company was not funding any GM work.

The global drug company Wyeth has tried another route, creating a protein called MYO-029 which disables myostatin. It plans to start trials in human patients shortly.

Dr Kambadur believes the molecule discovered at Ruakura might work better than the Wyeth one, blocking myostatin for longer and needing repeat injections only every few months.

He is now negotiating with Waikato Hospital to test myostatin levels in old people and in diabetes patients of various ethnic groups.

Dr Kambadur will report on his research at a three-yearly conference of the Muscular Dystrophy Association in Auckland next month.