For GDF11, "You could imagine that when it came out last year that it helped muscle, it was quite a surprise," says David Glass, executive director of the muscle diseases group at the Novartis Institutes for Biomedical Research in Cambridge, Massachusetts.
"Did we miss something?"
colleagues set out to determine why GDF11 had this apparent effect.
First, they tested the antibodies and other reagents that Wagers' group had used to measure GDF11 levels, and found that these chemicals could not distinguish between myostatin and GDF11.
When the Novartis
team used a more specific reagent to measure GDF11 levels in the blood of both rats and humans, they found that GDF11 levels actually increased with age - just as levels of myostatin do.
That contradicts what Wagers'
group had found.
team next used a combination of chemicals to injure a mouse's skeletal muscles, and then regularly injected the animal with three times as much GDF11 as Wagers
and her team had used.
Rather than regenerating the muscle, Glass
found, GDF11 seemed to make the damage worse by inhibiting the muscles' ability to repair themselves.
colleagues report their results on 19 May in Cell Metabolism4.
says that although his
group's results do not explain why parabiosis works, they could help to explain the mechanism behind bimagrumab, an experimental Novartis treatment for muscle weakness and wasting.
The drug, which is currently in clinical trials, blocks myostatin - and perhaps GDF11 as well.
Thomas Rando, a stem-cell biologist at Stanford University in California, praises the attention to detail in the methods used by Glass and his team.
Wagers' team in Harvard really did some pioneer work in this space, and Glass and his team in Novartis made further study and got some contradictory findings.