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16.06.2013

Animal study: a year of growth after just one anti-myostatin gene treatment

Pharmacists have called a halt to research on the first generation of myostatin inhibitors. They are effective, but steroids and growth hormone work better. Which is why doping gurus have turned their sights on the gene-therapy myostatin inhibitors. Researchers at the University of Pennsylvania are working on these, and they are past the stage of doing tests on mice and rats.

In 2000 American researchers published the results of an animal study in which they had genetically manipulated mice so that their cells started to produce dominant-negative myostatin [dnMS]. [FEBS Lett. 2000 May 26; 474(1): 71-5.] Dominant-negative myostatin deactivates the normal muscle-growth inhibiting myostatin and this intervention made the mice more muscular.

Myostatin expert Lee Sweeney and his colleagues are searching for effective genetic myostatin inhibitors for humans suffering from Duchenne muscular dystrophy and other muscle diseases. In 2010 they demonstrated that they could introduce anti-myostatin genes into mice with muscular dystrophy using manipulated adenoviruses. [PLoS One. 2010 Feb 11; 5(2): e9176.]

A year later, in 2011, Sweeney and his team showed that they had gone a step further. They introduced genes for dominant-negative myostatin, inserted in adenoviruses, into four Golden Retrievers suffering from a muscular disease using a drip. The dogs weighed 14-19 kg, a step closer to a bodybuilder human adult than a mouse. Three of the Golden Retrievers were given viruses that had not had anti-myostatin genes added. These were the control group.

Thirteen months after the intervention the dogs that had received gene therapy were a little heavier than the dogs in the control group. And it was primarily their muscles that had become heavier and bigger.

The researchers monitored the effect of the single therapy session using MRI technology.

The first two figures below show the total circumference of the extensor digitorum longus – muscle 1 in the figure at the top of the page [the human equivalent] – and the tibialis cranialis, muscle 2 in the figure at the top right of this page.

Below left you see how the muscles grew relatively fast during the first four months after the myostatin-inhibiting gene had been introduced. Muscle growth continued but at a slower rate during the rest of the year.

Looking at the figure above you'd wonder whether this study will result in a medicine against dystrophy. The researchers suspect that the approach needs to be combined with another – and pharmacists are not generally interested in combined approaches. Far too complicated in their opinion. But that Sweeney's viruses could lead to the development of interesting muscle strengthening possibilities is clear...

Source:
Hum Gene Ther. 2011 Dec;22(12):1499-509.

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