A John Hopkins scientist, who had shown in a previous study that the absence of the protein myostatin leads to oversized muscles in mice and men, has now found evidence that the overproduction of a protein called follistatin in mice lacking myostatin doubles the muscle-building effect.
According to Dr. Se-Jin Lee, a professor of molecular biology and genetics, his study shows that while mice that lack the gene that makes myostatin have roughly twice the amount of body muscle as normal, the rodents without myostatin that also overproduce follistatin have about four times as much muscle as normal counterparts.
Published in the online journal PLoS ONE, the new finding may significantly boost research efforts to "beef up" livestock or promote muscle growth in patients with muscular dystrophy and other wasting diseases.
When Dr. Lee gave follistatin to normal mice during the study, the rodents bulked up in the same way as would happen if the myostatin gene were turned off in the animals.
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, adding that these muscular mice averaged a 117 per cent increase in muscle fibre size and a 73 per cent increase in total muscle fibres 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. 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," added the researcher.
The new finding is of particular significance, says Dr. Lee, because 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.