The recent revival of interest in the way that the blood from younger animals (and people?) can improve the health of older ones came bundled with a particular protein candidate for the effect, GDF11. Several papers appeared on its effects in vivo, but there were people who found that odd, according to Nature News.
Those results quickly made GDF11 the leading explanation for the rejuvenating effects of transfusing young blood into old animals. But that idea was confusing to many because GDF11 is very similar to the protein myostatin, which prevents muscle stem cells from differentiating into mature muscle — the opposite effect to that seen by Wagers and her team.
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?”
Now in Cell Metabolism, Glass and co-workers are reporting that GDF11 does not, in fact, have the effects ascribed to it. If they’re right, this is (yet another) case of antibody trouble, because they report that the antibody used in the recent papers is not as selective as it’s supposed to be. Novartis has an anti-myostatin antibody in development as a therapeutic (which explains their immediate interest here) and they’re looking into whether it blocks GDF11 as well. Their paper suggests that that would be no bad thing, actually.
Amy Wagers and co-workers at Harvard, though, are apparently sticking to their guns, suggesting that there might be multiple forms of GDF11. That’s possible, to be sure, but it’s also (I hate to say this) the sort of rationale that one comes up with after one’s antibody has been called into question. I wouldn’t want to count the number of times that studies (large and small) have come undone because of antibody problems, and it’s almost always because they turn out to be less targeted than thought. There are a lot of proteins out there, and a lot of related proteins to any given target. Assaying an antibody against them can be quite tedious, but if you don’t, you run the risk of things suddenly getting the opposite of tedious, and not in a good way. We’ll see how the dust settles on this one.
If the Glass paper is correct, though, and GDF11 is not the answer, that throws the field wide open for someone to find out what the answer is. I would guess that several groups have held back getting into this area, thinking that the big prize had already been found, but if that’s not so, well. . .
Update: and as fate would have it, Nature News now has a feature on the problems of antibody reproducibility! Thanks to a post in the comments section for pointing this out.