Na myostatin nu follistatin...

[davy1010]

De wetenschap staat niet stil. Follistatin zorgt voor een verdubbeling van de spiermassa bij muizen.

BRON: Johns Hopkins Medical Institutions

"MIGHTY MICE” MADE MIGHTIER
Written by Johns Hopkins Medical Institutions
Wednesday, 29 August 2007



The Johns Hopkins scientist who first showed that the absence of the protein myostatin leads to oversized muscles in mice and men has now found a second protein, follistatin, whose overproduction in mice lacking myostatin doubles the muscle-building effect.

Results of Se-Jin Lee’s new study, appearing this Wednesday in PloS One, show that while mice that lack the gene that makes myostatin have roughly twice the amount of body muscle as normal, mice without myostatin that also overproduce follistatin have about four times as much muscle as normal mice.

Lee, M.D., Ph.D., a professor of molecular biology and genetics, says that this added muscle increase could significantly boost research efforts to “beef up” livestock or promote muscle growth in patients with muscular dystrophy and other wasting diseases.

Specifically, Lee first discovered that follistatin was capable of blocking myostatin activity in muscle cells grown under lab conditions. When he gave it to normal mice, the rodents bulked up, just as would happen if the myostatin gene in these animals was turned off.

He then genetically engineered a mouse that both lacked myostatin and made extra follistatin. If follistatin was increasing muscle growth solely by blocking myostatin, then Lee surmised that follistatin would have no added effect in the absence of myostatin.

“To my surprise and delight, there was an additive effect,” said Lee, who notes these muscular mice averaged a 117 percent increase in muscle fiber size and a 73 percent increase in total muscle fibers compared to normal mice.

“These findings show that the capacity for increasing muscle growth by targeting these pathways is much more extensive than we have appreciated,” adds Lee. “Now we’ll search for other players that cooperate with myostatin, so we can tap the full potential for enhancing muscle growth for clinical applications.”

Lee adds that this issue is of particular significance, as most agents targeting this pathway, including one drug being currently tested in a muscular dystrophy clinical trial, have been designed to block only myostatin and not other related proteins.

The research was funded by grants from the NIH and the Muscular Dystrophy Association and by a gift from Merck Research Laboratories.

[Tjok]

Ja maar eigenlijk is het enige interessante, kunnen we het ook bij mensen toepassen?

Die rechter muis ziet er trouwens wel uit als een lekker eiwitrijk hapje...

[jacky den bels]

zou wel iets zijn

[Taktix]

las hem elders & dacht hem hier even te posten. Staat er blijkbaar al .
Het zou voorlopig vooral interessant lijken om spierherstel e.d. na kanker/aids/... therapieën te bevorderen.

Maar in een aantal artikelen merk je onmiddellijk al de links naar bb & topsport:

Een nederlands (simpele) /artikel:
Elsevier.nl - Wetenschap - Supergespierde muis door spel met eiwitten

Supergespierde muis door spel met eiwitten

donderdag 30 augustus 2007 16:12

De bioloog Se-Jin Lee heeft een genetisch recept bedacht om de spiermassa van muizen in korte tijd te verviervoudigen. Voor mensen zou deze ontdekking het spierherstel bij ziektes als AIDS, kanker en Duchenne kunnen bevorderen.

Link: gespierde muis, rechts: gewone muis
De muis links is genetisch bewerkt, de muis rechts niet

Dat meldt het wetenschapsblad Nature (foto's). De gemuteerde muizen verschilden in twee opzichten genetisch van normale muizen. Ze zijn allereerst niet in staat om de proteïne myostatine te produceren (omdat dit gen door Lee is uitgeschakeld) en ze maken juist te veel aan van follistatine, ook een proteïne.

Verrast
Myostatine heeft de eigenschap om spierontwikkeling tegen te houden. Door het te verwijderen bleek echter ook dat het eiwit follistatine veel beter tot zijn recht kwam.

Lee was dan ook verrast dat de genetisch bewerkte muizen zoveel meer spieren ontwikkelden.

Niet alleen de spiervezels verdubbelden, ook de omvang de spieren in het algemeen nam met ruim 70 procent toe. Dit betekent voor mensen goed nieuws voor het spierherstel bij spierziekten, AIDS en kanker.

Medicijnen
Myostatine is bij mensen in veel mindere mate aanwezig, zegt Lee. Als er nu bij de mens een verwant eiwit gevonden kan worden, zou dat een enorme sprong voorwaarts zijn in de zoektocht naar medicijnen om spieren te versterken.Lee doelt dan met name op zieken, maar misschien vinden sporters en bodybuilders deze ontdekking ook nog wel interessant.

Tot nu toe hebben zulke pogingen nog niet veel succes opgeleverd. Volgens Lee komt door zijn bevindingen daar nu verandering in.

De bioloog is verbonden aan de medicijnafdeling van de John Hopkins University in de Amerikaanse stad Baltimore. De bevindingen van Lee zijn gepubliceerd op de website PlosOne.

Engelstalig:
http://www.nature.com/news/2007/0708.../070827-3.html

News
Published online: 29 August 2007; | doi:10.1038/news070827-3
Mighty mice could yield human treatments
Super-sized animals may pave way for new drugs and bigger livestock.

Michael Hopkin


Mutant mice (right) are massively more muscular than normal ones (left).
Se-Jin lee
It might sound like a cartoon scene from Tom and Jerry, but a biologist has come up with a real-life genetic recipe to create mice with four times more muscle than normal.

The mutant mice, created by Se-Jin Lee of Johns Hopkins University School of Medicine in Baltimore, Maryland, have two key genetic differences compared with normal mice. They cannot produce a protein called myostatin, and they produce too much of another protein, follistatin. Both changes boost muscle mass in mice.

The muscly mice differ significantly from normal mice — their muscle fibres are more than twice the size, and they have 73% more of them, Lee reports in the journal PLoS One1.

The fact that muscle mass was boosted in two ways — both the number and size of muscle fibres - is good news for medical researchers who are looking for ways to restore muscle in people with diseases such as muscular dystrophy, AIDS or cancer, Lee adds.

Double whammy

Myostatin restricts muscle development, which is why mice without this protein tend to bulk up. And follistatin binds to myostatin, possibly preventing its action, which is why Lee was investigating its effects. But he did not expect the mice to become so huge when given both treatments at once.

The fact that follistatin boosts muscle development in the absence of myostatin suggests that there is more than one mechanism. Mice also have higher levels of myostatin than people, notes Lee, suggesting that the protein is less important in humans. "In humans it's virtually undetectable — that's always left a nagging feeling," Lee says. "Clearly, there are other players."

If biologists can identify more proteins to which follistatin binds, it could spawn new and more-promising drugs for boosting muscle development in humans. So far, efforts to develop a drug that targets myostatin have not met with much success, although the drug company Wyeth is trialling an antibody-based treatment that could relieve muscular dystrophy by cancelling out myostatin's effects.

Muscle madness

Drugs to preserve human muscle mass could also help elderly people to avoid losing their muscle, Lee suggests. "It's not that people want to create 80-year-old Schwarzeneggers — it's just that elderly people get weak, and they can fall over and break their hip."

The discovery might also add to livestock breeders' idea of what creates muscular animals, which could help in breeding cattle or sheep that carry lots of meat. Several 'double-muscle' breeds, such as Belgian Blue cattle and Texel sheep, carry mutations in the myostatin gene.

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Genome Evolution and Structural Variation


The spectre of drug-enhanced sporting performance also looms over Lee's field of research. Clearly, any development that offers the prospect of more muscle growth will be tempting to athletes. Although no drug has yet been passed for human use to boost these muscle-development pathways, Lee says that there is no guarantee that people are not already experimenting with such compounds.

"I certainly wouldn't recommend it or attest to it even working," he says. "But there's this whole subculture [of risky drug-taking in sport] out there that's crazy. This will be an issue and will be a challenge [to regulatory authorities] for sure."